{"gene":"AGO1","run_date":"2026-06-09T22:02:42","timeline":{"discoveries":[{"year":2000,"finding":"AGO1 (Arabidopsis ARGONAUTE1) is required for post-transcriptional gene silencing (PTGS/cosuppression); loss-of-function ago1 mutants are defective in PTGS, placing AGO1 as an essential component of the plant RNA silencing machinery. A single amino acid conserved in AGO1, QDE-2, and RDE-1 is essential for PTGS activity.","method":"Forward genetic screen; sequencing of ago1 mutants; PTGS reporter assays in Arabidopsis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function with defined molecular phenotype, replicated across multiple alleles, conserved residue identified","pmids":["11016954"],"is_preprint":false},{"year":2002,"finding":"Hypomorphic ago1 mutants in Arabidopsis are defective for PTGS and hypersensitive to virus infection, demonstrating that PTGS is more sensitive than development to AGO1 perturbation, and that AGO1-mediated PTGS functions as an antiviral defense mechanism.","method":"Genetic analysis of hypomorphic ago1 alleles; PTGS assays; virus infection assays","journal":"The Plant cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple hypomorphic alleles, orthogonal phenotypic readouts (PTGS efficiency and virus susceptibility), replicated genetic epistasis","pmids":["11910010"],"is_preprint":false},{"year":2006,"finding":"Arabidopsis AGO1 encodes the RNA slicer enzyme of the miRNA pathway; AGO1-catalyzed mRNA cleavage of AGO1 mRNA is directed by miR168, and AGO1 preferentially stabilizes miR168 relative to other miRNAs, establishing an AGO1 homeostasis feedback loop. Disruption of any regulatory process disturbs miRNA pathway function.","method":"Genetic analysis of MIR168 and AGO1 mutants/transgenes; miRNA quantification; mRNA cleavage assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal genetic approaches, direct measurement of slicer activity and miRNA levels, clearly defined feedback mechanism","pmids":["16600876"],"is_preprint":false},{"year":2006,"finding":"Human AGO1 (hAGO1/EIF2C1) and AGO2 associate with gene promoter DNA in cells treated with antigene RNAs (agRNAs), mediating transcriptional silencing at promoters in the nucleus. Inhibiting AGO1 expression reverses both transcriptional and post-transcriptional silencing.","method":"Chromatin immunoprecipitation (ChIP); RNAi knockdown of AGO1/AGO2; gene expression assays in mammalian cells","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus knockdown rescue, single lab, two orthogonal methods","pmids":["16936728"],"is_preprint":false},{"year":2008,"finding":"The miR173-AGO1 complex in Arabidopsis has unique functionality required to initiate phased siRNA (tasiRNA) formation from TAS1 and TAS2 loci; a single miR173 target site is sufficient to route transcripts into the tasiRNA pathway, and this activity is distinct from other miRNA-AGO1 complexes.","method":"Genetic complementation with modified TAS loci; syn-tasiRNA reporter assays; co-immunoprecipitation of miR173-AGO1 complex","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reconstitution with modified loci, co-IP, single lab with multiple orthogonal approaches","pmids":["19066226"],"is_preprint":false},{"year":2009,"finding":"In Arabidopsis, ZLL (ZWILLE/PINHEAD/AGO10) negatively regulates AGO1 at the protein level (not mRNA level); loss of ZLL in ago1 hypomorphic mutants increases AGO1 protein. The PAZ domain of AGO1 (involved in small RNA binding) is interchangeable between AGO1 and ZLL, while the MID and PIWI domains (involved in 5'-end selectivity and mRNA cleavage) and the N-terminal domain confer functional specificity.","method":"Genetic double-mutant analysis; protein level quantification; domain-swap experiments between AGO1 and ZLL","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — domain swap experiments plus genetic epistasis, multiple alleles, two orthogonal methods in single lab","pmids":["19763164"],"is_preprint":false},{"year":2009,"finding":"Human AGO1 (EIF2C1) can mediate siRNA-directed mRNA degradation independently of AGO2 slicer activity; off-target and a portion of on-target siRNA-mediated mRNA degradation requires siRNA interaction with AGO1 or AGO2 and the RISC-loading complex but is independent of AGO2 cleavage.","method":"Antisense-mediated reduction of AGO proteins; AGO2 knockout cell lines; modified siRNAs; P-body protein depletion assays","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO cell lines plus antisense knockdown, multiple approaches, single lab","pmids":["19767612"],"is_preprint":false},{"year":2010,"finding":"In fission yeast (S. pombe), Ago1 amino terminus binds 14-3-3 proteins; overexpression of the Ago1 N-terminus delays cell cycle at the G2/M boundary by inhibiting nuclear import of the mitosis-inducing phosphatase Cdc25, leading to constitutive phosphorylation of Cdc2 on tyrosine 15.","method":"Pulldown/co-immunoprecipitation of Ago1 with 14-3-3 proteins; overexpression of Ago1 N-terminus; Cdc25 localization assays; Cdc2 phosphorylation assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus functional overexpression with defined biochemical readouts, single lab","pmids":["17043360"],"is_preprint":false},{"year":2010,"finding":"S. pombe Ago1 (and Dcr1, but not Rdp1) is required for cell cycle checkpoint enactment (regulated Cdc2 hyperphosphorylation) upon genotoxic stress, cytokinesis, and mating, demonstrating functions independent of RNAi-mediated heterochromatin formation. Human AGO2 (hGERp95/EIF2C2/hAgo2) compensates for loss of ago1+ in fission yeast, suggesting conserved cell cycle functions.","method":"Null mutant analysis of ago1+, dcr1+, rdp1+ in S. pombe; epistasis; Cdc2 phosphorylation assays; complementation with human AGO2","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with null mutants, biochemical readout, cross-species complementation, single lab","pmids":["14699070"],"is_preprint":false},{"year":2010,"finding":"The kinesin motor Cut7 interacts with Ago1-containing RNPs in S. pombe and is required for biogenesis and/or stability of Ago1-containing cytoplasmic RNP complexes; Cut7 also interacts with Dcr1 and Rdp1 (Ago1 cognate binding proteins). Loss of Cut7 activity leads to increased centromeric transcripts consistent with PTGS defects.","method":"Genetic screen; pulldown and co-immunoprecipitation; microscopy of RNP complexes; centromeric transcript analysis","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP plus genetic screen and functional readout, single lab","pmids":["19883398"],"is_preprint":false},{"year":2011,"finding":"Arabidopsis AGO1 and AGO2 act redundantly in miR408-mediated regulation of Plantacyanin; neither single ago1 nor ago2 mutant abolishes this regulation, but the ago1 ago2 double mutant is compromised, showing overlapping specificity beyond the 5'-nucleotide rule.","method":"Genetic analysis of single and double ago1/ago2 mutants; miR408 target expression assays; complementation with 5'A and 5'U MIR408 transgenes","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with double mutants plus complementation, single lab","pmids":["22174881"],"is_preprint":false},{"year":2011,"finding":"The miRNA pathway limits AGO1 availability for siRNA-mediated PTGS defense against exogenous RNA in plants; plants supporting transgene PTGS exhibit increased AGO1 protein, and impairing miR168-directed regulation of AGO1 mRNA increases PTGS efficiency. Competition between siRNAs and miRNAs for AGO1 binding modulates PTGS efficiency.","method":"Transgene PTGS assays; AGO1 protein level quantification; genetic manipulation of miRNA pathway components; miR168-AGO1 mRNA interaction analysis","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple genetic and molecular approaches, single lab, mechanistic model supported by protein quantification","pmids":["21813456"],"is_preprint":false},{"year":2012,"finding":"The viral F-box protein P0 (from enamovirus PEMV-1 and poleroviruses) destabilizes AGO1 through an F-box-like domain; this mechanism is conserved between phylogenetically unrelated viral suppressors, indicating AGO1 is a primary target of viral counter-silencing strategies.","method":"Transient silencing suppression assays; AGO1 protein level analysis in P0-expressing plants; F-box domain mutants","journal":"Virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional suppression assays plus domain mutants, single lab, two viral systems","pmids":["22361475"],"is_preprint":false},{"year":2013,"finding":"Human AGO1 (EIF2C1) directly interacts with RNA Polymerase II in the nucleus and associates with promoters of transcriptionally active genes genome-wide; nuclear AGO1 regulates expression of AGO1-bound genes implicated in oncogenic pathways including cell cycle progression.","method":"ChIP-seq; co-immunoprecipitation of AGO1 with RNA Pol II; biochemical fractionation; gene expression analysis","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — ChIP-seq with biochemical co-IP, multiple orthogonal methods, genome-wide landscape in human cancer cells","pmids":["24086155"],"is_preprint":false},{"year":2014,"finding":"Arabidopsis AGO1 interacts with the miRNA nucleotidyl transferase HESO1 through its PAZ and PIWI domains; HESO1 can uridylate AGO1-bound miRNAs in vitro, and uridylation of 5' RNA fragments produced by miRNA-mediated cleavage is also AGO1-associated. Methylation by HEN1 protects miRNAs from this AGO1-associated HESO1 activity.","method":"Co-immunoprecipitation of AGO1-HESO1; in vitro uridylation assay with purified HESO1 and AGO1-bound miRNAs; genetic analysis of hen1 mutants","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of enzymatic activity, co-IP, genetic mutant analysis; single lab but multiple orthogonal methods","pmids":["24733911"],"is_preprint":false},{"year":2014,"finding":"In mammals, novel small RNAs derived from tandem genomic loci associate exclusively with AGO1 but not AGO2, and their expression depends on AGO1 protein levels; knockdown of AGO1 dramatically reduces these AGO1-specific sRNAs, demonstrating that a sorting mechanism for the AGO1-4 family is functional in mammals.","method":"Immunoprecipitation followed by deep sequencing (IP-seq) of AGO1 and AGO2 from EBV-infected cells; AGO1 knockdown; target mRNA regulation assays","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal IP-seq plus knockdown validation, single lab","pmids":["24627180"],"is_preprint":false},{"year":2018,"finding":"AGO1 contains a degron motif within its DUF1785 domain required for interaction with the SCF-P0 ubiquitin ligase complex and subsequent proteasomal degradation. A single point mutation in the DUF1785 domain (ago1-57) impairs RNA duplex unwinding of siRNA duplexes (but not miRNA duplexes), revealing that DUF1785 is required for RISC loading via siRNA strand separation, and is essential for phased siRNA production and sense transgene PTGS.","method":"Forward genetic suppressor screen; cell-free RISC reconstitution assay; in vitro RNA unwinding assay; site-directed mutagenesis; co-immunoprecipitation with SCF-P0","journal":"The Plant cell","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cell-free reconstitution, in vitro unwinding assay, mutagenesis, and co-IP in single lab with multiple orthogonal methods","pmids":["29848768"],"is_preprint":false},{"year":2019,"finding":"Arabidopsis AGO1 and P0 (viral suppressor of RNA silencing from TuYV) associate on the endoplasmic reticulum (ER); P0-mediated AGO1 degradation proceeds via an ATG5- and ATG7-dependent autophagic pathway, with ATI1 and ATI2 as ER-associated proteins that interact with both P0 and AGO1 and mediate loading into ER-associated vesicles transported to the vacuole.","method":"Co-immunoprecipitation; subcellular fractionation; confocal microscopy; ATG mutant analysis; ATI1/ATI2 interaction assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — co-IP, live imaging, genetic knockouts (atg5, atg7, ati1, ati2), multiple orthogonal approaches, single lab","pmids":["31628252"],"is_preprint":false},{"year":2019,"finding":"In Arabidopsis, a large pool of cytoplasmic mature miRNAs exists unbound to AGO1; miRNAs show highly different RISC-loading efficiencies determined by information in their precursors; AGO1 protein availability is a limiting factor for miRNA loading efficiency.","method":"Size-exclusion fractionation of cell extracts; high-throughput sequencing of small RNA pools; transient and transgenic expression of selected miRNAs; AGO1 overexpression","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — fractionation plus sequencing plus genetic manipulation, single lab","pmids":["31392979"],"is_preprint":false},{"year":2019,"finding":"Translational readthrough of human AGO1 mRNA, promoted by let-7a miRNA acting on a cis-sequence downstream of the canonical stop codon, generates a C-terminally extended isoform Ago1x. Ago1x can load miRNAs onto target mRNAs but lacks the ability to interact with GW182, preventing downstream silencing, so it functions as a competitive inhibitor of the canonical miRNA pathway.","method":"Reporter assays for translational readthrough; ribosome profiling data analysis; mass spectrometry; specific antibody detection; GW182 interaction assays; global translation measurement","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro and in vivo reporter assays, mass spectrometry, ribosome profiling, interaction assays, multiple orthogonal methods in single lab","pmids":["31330067"],"is_preprint":false},{"year":2020,"finding":"CARP9, a nuclear-localized intrinsically disordered protein, bridges HYL1 to AGO1 in the nucleus to promote miRNA loading into AGO1. CARP9 interacts with HYL1 and AGO1 (but not other miRNA biogenesis factors), promotes HYL1-AGO1 interaction, stabilizes AGO1 and mature miRNAs, and deficiency in CARP9 results in reduced AGO1-loaded miRNAs and partial nuclear retention of miRNA.","method":"Co-immunoprecipitation of CARP9-HYL1 and CARP9-AGO1; miRNA loading assays; nuclear fractionation; genetic loss-of-function of CARP9","journal":"Plant physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, fractionation, genetic mutant analysis, single lab with multiple approaches","pmids":["32636339"],"is_preprint":false},{"year":2020,"finding":"In mouse endothelial cells, AGO1 (EIF2C1) suppresses thrombospondin-1 (THBS1/TSP1) via the miRNA pathway identified by CLIP-seq; endothelial-specific AGO1 deletion leads to inhibition of TSP1, increased vascularity, adipose tissue browning, improved insulin sensitivity, and metabolic benefits. TSP1 overexpression in AGO1-KO mice substantially attenuates these beneficial effects.","method":"EC-conditional AGO1 knockout mice; CLIP-seq (crosslinking immunoprecipitation-sequencing); metabolic phenotyping; TSP1 rescue experiments","journal":"Circulation","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO in vivo with CLIP-seq, rescue experiments, multiple metabolic phenotypic readouts","pmids":["32393053"],"is_preprint":false},{"year":2020,"finding":"Brassinosteroids (BRs) inhibit miRNA-mediated translational repression by reducing AGO1 localization at the endoplasmic reticulum (ER) in Arabidopsis; ROT3 (a BR biosynthesis enzyme) co-localizes with AGO1 at the ER and interacts with AGO1 in a GW motif-dependent manner; the AGO1-ROT3 interaction is necessary for ROT3 function.","method":"Subcellular fractionation; live cell imaging; co-immunoprecipitation of AGO1-ROT3; GW motif mutant analysis; BR treatment/mutant plants with translational repression readout","journal":"Journal of integrative plant biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, localization imaging, GW motif mutagenesis, single lab","pmids":["34020507"],"is_preprint":false},{"year":2021,"finding":"Human AGO1 (EIF2C1) controls skeletal muscle differentiation by regulating global H3K27 acetylation via modulation of the interaction between enhancer RNAs (eRNAs) and the CBP acetyltransferase, thereby enabling developmental enhancer activation. AGO1 depletion blocks CBP acetyltransferase activation and blocks the myogenic program including MyoD and downstream myogenic gene activation.","method":"AGO1 depletion (knockdown/KO) during myogenic differentiation; ChIP for H3K27ac; eRNA-CBP interaction assays; RNA-seq; ChIP-seq","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-seq, interaction assays, loss-of-function with defined molecular mechanism, single lab","pmids":["34852230"],"is_preprint":false},{"year":2021,"finding":"A secretory fungal effector VdSSR1 from Verticillium dahliae translocates to the plant nucleus and sequesters ALY family proteins (adaptors of the TREX complex) to interfere with nuclear export of the AGO1-miRNA complex, reducing cytoplasmic AGO1 and sRNA levels and thereby suppressing transkingdom antifungal RNAi.","method":"Co-immunoprecipitation of VdSSR1 with ALY proteins; AGO1 localization assays; sRNA quantification; virulence assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, protein localization, sRNA quantification, functional virulence readout, single lab","pmids":["35290117"],"is_preprint":false},{"year":2022,"finding":"AGO1 regulates pericentromeric heterochromatin in mouse embryonic stem cells; AGO1 depletion causes redistribution of repressive histone mark H3K9me3 and HP1α away from pericentromeric regions, and major satellite transcripts are strongly upregulated in Ago1_KO mESCs. Specific miRNAs with complementarity to major satellites can partially regulate these transcripts.","method":"AGO1 knockout in mESCs; ChIP for H3K9me3 and HP1α; major satellite transcript quantification; AGO1 rescue experiments; Drosha KO comparison","journal":"Life science alliance","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO with defined chromatin phenotype, rescue validation, single lab with multiple readouts","pmids":["35236760"],"is_preprint":false},{"year":2024,"finding":"In mouse embryonic stem cells (mESCs), AGO1 (EIF2C1) controls stemness independently of its RNA-binding activity through facilitating protein folding: AGO1 specifically interacts with HOP (a co-chaperone for HSP70/HSP90) and enhances folding of HOP client proteins with intrinsically disordered regions. This is an RNA-independent function divergent from AGO2's differentiation-promoting miRNA pathway function.","method":"AGO1 KO in mESCs; co-immunoprecipitation of AGO1 with HOP; protein folding assays; small RNA independence demonstrated by mutants; stem cell fate assays","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — co-IP, KO with defined cellular phenotype, RNA-independence demonstrated, novel mechanism, single lab with multiple orthogonal methods","pmids":["38458189"],"is_preprint":false},{"year":2024,"finding":"AGO2 represses AGO1 mRNA expression in mESCs via a conserved let-7 miRNA-binding site in the AGO1 3' UTR; mutation of this binding site at the endogenous locus abolishes AGO2-mediated repression of AGO1 mRNA and compromises exit from pluripotency, establishing a cross-regulatory mechanism between AGO1 and AGO2.","method":"Loss-of-function and gain-of-function approaches in mESCs; endogenous mutagenesis of let-7 binding site in AGO1 3' UTR; AGO1 mRNA quantification; pluripotency exit assays","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — endogenous site mutagenesis, gain/loss-of-function, functional pluripotency readout, single lab","pmids":["40132882"],"is_preprint":false},{"year":2024,"finding":"Human AGO1 NDD-associated mutations (modeled in C. elegans alg-1) cause antimorphic (dominant negative) effects on miRNA processing, miRISC formation, and target repression; mutant ALG-1 proteins likely sequester functional miRISC components into non-functional complexes. Allele-specific disruptions in mature miRNA profiles and downstream translational efficiency/mRNA abundance are observed.","method":"Knock-in of human AGO1 NDD mutations into C. elegans alg-1; miRNA profiling; translational efficiency measurement; gene expression analysis; dominant-negative epistasis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — precise knock-in genetics, multiple alleles, miRNA profiling, ribosome/translation readouts, cross-clade complementation approach","pmids":["38412125"],"is_preprint":false},{"year":2025,"finding":"HC-Pro (viral suppressor from Turnip mosaic virus) inhibits HEN1 methyltransferase activity and recruits HEN1, ATG8a, and indirectly AGO1 into HC-Pro bodies (H-bodies), leading to autophagic degradation of AGO1 and accumulation of unmethylated miRNA duplexes and impairment of RISC assembly. Inhibition of HEN1 correlates with autophagic degradation of AGO1.","method":"FRET analysis of HC-Pro bodies; transgenic plant analysis; AGO1 protein level quantification; unMet-miRNA profiling; genetic analysis of hen1 and heso1 mutants","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FRET, transgenic analysis, genetic epistasis, single lab with multiple readouts","pmids":["40082396"],"is_preprint":false},{"year":2025,"finding":"Nuclear AGO1 (EIF2C1) in endothelial cells acts as a transcriptional coactivator of NF-κB by directly interacting with NF-κB p65, enhancing transcription of pro-inflammatory genes including ICAM1 and THBS1. EC-specific AGO1 deletion in mice reduces vascular inflammation, improves lipid metabolism, and attenuates atherosclerosis.","method":"EC-conditional AGO1 KO mice with atherosclerosis model; Cut&Tag sequencing; ChIP assays; co-IP of AGO1 with NF-κB p65; RNA-seq; monocyte adhesion assay; ASO-based therapeutic knockdown","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, ChIP/Cut&Tag, conditional KO in vivo with functional readouts; preprint, not peer-reviewed","pmids":["40654672"],"is_preprint":true},{"year":2025,"finding":"In mESCs, AGO1 is localized primarily in the nucleus of neural progenitor cells (NPCs) and binds the LIN28A promoter region to inhibit LIN28A transcription; AGO1 KO results in loss of NPC polarity via increased LIN28A, which reduces REELIN expression by binding REELIN mRNA; LIN28A knockdown or recombinant REELIN treatment rescues the polarity defect.","method":"AGO1 KO in mouse brain and human forebrain organoids; ChIP for AGO1 at LIN28A promoter; LIN28A-REELIN mRNA interaction assays; nuclear localization microscopy; LIN28A knockdown rescue","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP, KO organoid model, rescue experiments, multiple readouts; preprint, not peer-reviewed","pmids":["bio_10.1101_2025.10.01.679670"],"is_preprint":true},{"year":2025,"finding":"AGO1 physically interacts with the lncRNA NEAT1 and key paraspeckle proteins (PSPs) in the nucleus and co-localizes with paraspeckles; AGO1 depletion disrupts both NEAT1 isoform expression, reduces PSP-NEAT1 interactions, and impairs paraspeckle formation. Conversely, NEAT1 depletion mis-localizes AGO1 from paraspeckles and alters active chromatin compartments.","method":"Co-immunoprecipitation of AGO1 with NEAT1 and PSPs; confocal microscopy co-localization; AGO1 and NEAT1 depletion experiments; nuclear fractionation","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-IP and co-localization in single preprint without peer review; preliminary mechanistic follow-up","pmids":["bio_10.1101_2025.01.26.634929"],"is_preprint":true},{"year":1999,"finding":"The human EIF2C1 gene (AGO1) consists of 19 exons spanning ~50 kb, is located at chromosome 1p34-p35, is ubiquitously expressed at low-to-medium levels, and belongs to a multigene family sharing ~70% identity with plant AGO1, establishing it as a member of the conserved Argonaute family.","method":"cDNA cloning; genomic organization; chromosomal localization by fluorescence in situ hybridization; Northern blot expression analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cloning, FISH localization, expression analysis; foundational gene characterization paper","pmids":["10534406"],"is_preprint":false}],"current_model":"Human AGO1 (EIF2C1/hAGO1) is a multi-functional Argonaute protein that serves as a core component of the RNA-induced silencing complex (RISC), associating with miRNAs and siRNAs to mediate post-transcriptional gene silencing via mRNA cleavage and translational repression; in the nucleus, it directly interacts with RNA Polymerase II and NF-κB p65 to regulate transcription of active genes and pro-inflammatory targets, maintains pericentromeric heterochromatin in embryonic stem cells, and controls cell fate (stemness) through an RNA-independent mechanism involving interaction with the HSP70/HSP90 co-chaperone HOP to facilitate protein folding of intrinsically disordered client proteins. AGO1 homeostasis is maintained by miR168-directed autoregulation and cross-regulation by AGO2 via let-7, while its levels are also controlled by viral suppressors (P0, HC-Pro) that target it for autophagic degradation through the endoplasmic reticulum, and by the DUF1785 domain which is required for siRNA duplex unwinding during RISC loading."},"narrative":{"mechanistic_narrative":"AGO1 is a core Argonaute protein that binds small RNAs to direct post-transcriptional gene silencing, and which has acquired additional nuclear transcriptional and RNA-independent chaperone functions across eukaryotes [PMID:11016954, PMID:16600876, PMID:24086155, PMID:38458189]. In its canonical role it acts as the slicer enzyme of the miRNA pathway and an essential effector of antiviral PTGS, with siRNA-versus-miRNA competition and small-RNA sorting partitioning distinct substrate pools to AGO1 [PMID:11016954, PMID:11910010, PMID:16600876, PMID:24627180]. RISC loading requires the DUF1785 domain for siRNA duplex unwinding, while the MID and PIWI domains confer 5'-end selectivity and cleavage specificity, and human AGO1 can mediate siRNA-directed mRNA degradation independently of AGO2 slicer activity [PMID:19763164, PMID:19767612, PMID:29848768]. AGO1 abundance is tightly homeostatic: it is autoregulated through miR168-directed cleavage of its own mRNA, cross-regulated by AGO2 via a let-7 site in its 3' UTR, and targeted for degradation by viral suppressors P0 (SCF-mediated) and HC-Pro through an ATG5/ATG7-dependent autophagic route at the endoplasmic reticulum [PMID:16600876, PMID:21813456, PMID:29848768, PMID:31628252, PMID:40132882, PMID:40082396]. In the nucleus, human AGO1 directly interacts with RNA Polymerase II at active promoters and acts as a transcriptional coactivator of NF-κB p65 to drive pro-inflammatory genes, and it maintains pericentromeric heterochromatin marked by H3K9me3 and HP1α in embryonic stem cells [PMID:24086155, PMID:35236760, PMID:40654672]. Beyond RNA-based silencing, AGO1 controls stem cell fate independently of small-RNA binding by interacting with the HSP70/HSP90 co-chaperone HOP to promote folding of intrinsically disordered client proteins [PMID:38458189]. In vivo, endothelial AGO1 suppresses thrombospondin-1 via the miRNA pathway, influencing vascular and metabolic phenotypes [PMID:32393053]. Dominant-negative AGO1 mutations modeled in C. elegans disrupt miRISC formation and target repression, linking AGO1 to neurodevelopmental disorders [PMID:38412125].","teleology":[{"year":2000,"claim":"Established AGO1 as an essential, genetically required component of the RNA silencing machinery, defining the biological process it serves before its molecular activity was known.","evidence":"Forward genetic screen and PTGS reporter assays in Arabidopsis ago1 mutants","pmids":["11016954"],"confidence":"High","gaps":["Did not define AGO1's biochemical activity","Conserved residue function not mechanistically resolved"]},{"year":2002,"claim":"Showed AGO1-mediated PTGS functions as an antiviral defense and is more dose-sensitive than developmental roles, separating its silencing and developmental functions.","evidence":"Genetic analysis of hypomorphic ago1 alleles with PTGS and virus infection assays in Arabidopsis","pmids":["11910010"],"confidence":"High","gaps":["Molecular basis of antiviral specificity unresolved","No direct biochemical activity assayed"]},{"year":2006,"claim":"Identified AGO1 as the slicer enzyme of the miRNA pathway and uncovered miR168-directed autoregulation, providing the central homeostatic logic of AGO1 abundance.","evidence":"Genetic analysis of MIR168/AGO1, miRNA quantification, and mRNA cleavage assays in Arabidopsis","pmids":["16600876"],"confidence":"High","gaps":["Structural basis of slicer catalysis not addressed","Preferential miR168 stabilization mechanism unresolved"]},{"year":2006,"claim":"Demonstrated human AGO1 functions in the nucleus at promoters to mediate transcriptional silencing, extending Argonaute function beyond cytoplasmic mRNA regulation.","evidence":"ChIP and RNAi knockdown with gene expression assays in mammalian cells","pmids":["16936728"],"confidence":"Medium","gaps":["Single lab","Direct chromatin recruitment mechanism not defined"]},{"year":2009,"claim":"Mapped domain-level functional specialization, assigning small-RNA binding to PAZ and cleavage/5'-selectivity to MID/PIWI, and revealed protein-level regulation of AGO1 by ZLL/AGO10.","evidence":"Genetic double-mutant analysis and domain-swap experiments between AGO1 and ZLL in Arabidopsis","pmids":["19763164"],"confidence":"High","gaps":["Mechanism of ZLL-mediated protein regulation unresolved","N-terminal domain specificity determinants not defined"]},{"year":2009,"claim":"Showed human AGO1 can mediate siRNA-directed mRNA degradation independently of AGO2 slicer activity, establishing functional non-redundancy among human Argonautes.","evidence":"Antisense knockdown, AGO2 KO cell lines and modified siRNAs in human cells","pmids":["19767612"],"confidence":"Medium","gaps":["Degradation mechanism without slicing unresolved","RISC-loading complex requirements only partially defined"]},{"year":2010,"claim":"Revealed RNAi-independent cell-cycle functions of Ago1, linking its N-terminus to 14-3-3 binding, Cdc25 import, and checkpoint enactment under genotoxic stress.","evidence":"Co-IP, N-terminus overexpression, Cdc2 phosphorylation and checkpoint assays in S. pombe with human AGO2 complementation","pmids":["17043360","14699070"],"confidence":"Medium","gaps":["Mechanistic link between Ago1 and Cdc25 import indirect","Relevance to mammalian AGO1 not tested"]},{"year":2010,"claim":"Identified the kinesin Cut7 as required for biogenesis/stability of Ago1-containing cytoplasmic RNPs, connecting Ago1 effector complexes to cytoskeletal trafficking.","evidence":"Genetic screen, reciprocal co-IP, microscopy and centromeric transcript analysis in S. pombe","pmids":["19883398"],"confidence":"Medium","gaps":["Direct vs indirect Cut7-Ago1 association unresolved","Conservation in mammals untested"]},{"year":2014,"claim":"Defined AGO1-associated small-RNA quality control through HESO1-mediated uridylation of AGO1-bound miRNAs, counteracted by HEN1 methylation.","evidence":"Co-IP, in vitro uridylation reconstitution, and hen1 mutant analysis in Arabidopsis","pmids":["24733911"],"confidence":"High","gaps":["In vivo turnover consequences of uridylation only partly defined","Domain contacts for HESO1 binding not structurally mapped"]},{"year":2014,"claim":"Demonstrated active small-RNA sorting in mammals, with specific sRNA classes loaded exclusively into AGO1, reinforcing functional divergence among Argonautes.","evidence":"AGO1/AGO2 IP-seq and AGO1 knockdown in EBV-infected human cells","pmids":["24627180"],"confidence":"Medium","gaps":["Sorting determinants not defined","Functional output of AGO1-specific sRNAs limited"]},{"year":2013,"claim":"Established that nuclear human AGO1 directly binds RNA Pol II and associates with active promoters genome-wide, defining a transcriptional regulatory role at oncogenic gene programs.","evidence":"ChIP-seq, co-IP with RNA Pol II, and fractionation in human cancer cells","pmids":["24086155"],"confidence":"High","gaps":["Mechanism of promoter selectivity unresolved","Whether small RNAs guide nuclear AGO1 not settled"]},{"year":2016,"claim":"Clarified that AGO1 abundance limits siRNA-versus-miRNA partitioning and PTGS efficiency, integrating miR168 autoregulation into antiviral defense capacity.","evidence":"Transgene PTGS assays with AGO1 protein quantification and miRNA-pathway manipulation in plants","pmids":["21813456"],"confidence":"Medium","gaps":["Quantitative competition parameters not defined","Tissue-specific differences unaddressed"]},{"year":2018,"claim":"Assigned the DUF1785 domain a dual role as a siRNA-unwinding module for RISC loading and a degron for SCF-P0-mediated degradation, mechanistically separating siRNA from miRNA duplex handling.","evidence":"Suppressor screen, cell-free RISC reconstitution, in vitro unwinding, mutagenesis and SCF-P0 co-IP in Arabidopsis","pmids":["29848768"],"confidence":"High","gaps":["Structural basis of strand separation unresolved","Why miRNA duplexes are exempt not fully explained"]},{"year":2019,"claim":"Defined the route of viral P0-driven AGO1 turnover as ER-associated autophagy requiring ATG5/ATG7 and ATI1/ATI2, localizing AGO1 degradation to ER-derived vesicles.","evidence":"Co-IP, fractionation, confocal imaging and atg/ati mutant analysis in Arabidopsis","pmids":["31628252"],"confidence":"High","gaps":["Trigger for ER recruitment unresolved","Selectivity of autophagic cargo loading not fully defined"]},{"year":2019,"claim":"Showed AGO1 protein availability limits miRNA loading and that a large unbound cytoplasmic miRNA pool exists, with precursor-encoded determinants of loading efficiency.","evidence":"Size-exclusion fractionation, small-RNA sequencing and AGO1 overexpression in Arabidopsis","pmids":["31392979"],"confidence":"Medium","gaps":["Precursor features dictating loading not enumerated","Fate of unloaded miRNAs unresolved"]},{"year":2019,"claim":"Identified a let-7-promoted readthrough isoform Ago1x that loads miRNAs but cannot recruit GW182, functioning as a competitive inhibitor of canonical silencing in humans.","evidence":"Readthrough reporters, ribosome profiling, mass spectrometry and GW182 interaction assays in human cells","pmids":["31330067"],"confidence":"High","gaps":["Physiological abundance and contexts of Ago1x not fully mapped","Regulation of readthrough beyond let-7 unclear"]},{"year":2020,"claim":"Showed nuclear miRNA loading into AGO1 is promoted by the disordered bridge protein CARP9 linking HYL1 to AGO1, defining a nuclear loading checkpoint in plants.","evidence":"Co-IP, nuclear fractionation, loading assays and CARP9 loss-of-function in Arabidopsis","pmids":["32636339"],"confidence":"Medium","gaps":["Structural basis of bridging unresolved","Conservation in animals untested"]},{"year":2020,"claim":"Linked endothelial AGO1 to in vivo metabolic and vascular phenotypes through miRNA-mediated suppression of TSP1.","evidence":"EC-conditional AGO1 KO mice, CLIP-seq, metabolic phenotyping and TSP1 rescue","pmids":["32393053"],"confidence":"High","gaps":["Direct miRNA-target topology only inferred","Tissue specificity of effect not fully dissected"]},{"year":2021,"claim":"Connected BR signaling to miRNA activity by showing BRs reduce AGO1 ER localization through GW-motif-dependent ROT3 interaction, regulating translational repression.","evidence":"Fractionation, imaging, co-IP and GW-motif mutagenesis in Arabidopsis","pmids":["34020507"],"confidence":"Medium","gaps":["Mechanism coupling ER localization to repression unresolved","Direct vs indirect ROT3 effects not separated"]},{"year":2021,"claim":"Revealed a chromatin-level role for AGO1 in enabling enhancer activation via eRNA-CBP interaction and H3K27 acetylation during muscle differentiation.","evidence":"AGO1 loss-of-function, H3K27ac ChIP, eRNA-CBP assays and RNA/ChIP-seq in myogenic cells","pmids":["34852230"],"confidence":"Medium","gaps":["Whether small RNAs guide this function unresolved","Direct AGO1-eRNA-CBP contacts not structurally defined"]},{"year":2022,"claim":"Showed AGO1 maintains pericentromeric heterochromatin in mammalian stem cells, with depletion redistributing H3K9me3/HP1α and derepressing satellite transcripts.","evidence":"AGO1 KO in mESCs, H3K9me3/HP1α ChIP, satellite transcript quantification and rescue","pmids":["35236760"],"confidence":"Medium","gaps":["miRNA dependence only partial","Mechanism of HP1α/H3K9me3 targeting unresolved"]},{"year":2024,"claim":"Defined an RNA-independent function for AGO1 in stemness via interaction with the HOP co-chaperone to fold intrinsically disordered clients, diverging from AGO2's miRNA-based differentiation role.","evidence":"AGO1 KO in mESCs, AGO1-HOP co-IP, protein folding assays and RNA-independence mutants","pmids":["38458189"],"confidence":"High","gaps":["Client repertoire incompletely defined","Structural basis of AGO1-HOP coupling unresolved"]},{"year":2024,"claim":"Established AGO2-to-AGO1 cross-regulation through a conserved let-7 site in the AGO1 3' UTR controlling exit from pluripotency.","evidence":"Endogenous let-7 site mutagenesis with gain/loss-of-function and pluripotency assays in mESCs","pmids":["40132882"],"confidence":"Medium","gaps":["Quantitative contribution to AGO1 dosage unresolved","Conservation across lineages untested"]},{"year":2024,"claim":"Connected AGO1 to neurodevelopmental disease by showing patient mutations act dominant-negatively to sequester miRISC components and disrupt target repression.","evidence":"Knock-in of human AGO1 NDD mutations into C. elegans alg-1 with miRNA profiling and translation readouts","pmids":["38412125"],"confidence":"High","gaps":["Mechanism validated in invertebrate model","Affected human neuronal pathways not directly mapped"]},{"year":2025,"claim":"Defined nuclear AGO1 as an NF-κB p65 coactivator driving pro-inflammatory transcription and atherosclerosis in endothelium.","evidence":"EC-conditional AGO1 KO mice, Cut&Tag, ChIP, p65 co-IP and ASO knockdown (preprint)","pmids":["40654672"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Direct vs indirect chromatin recruitment unresolved"]},{"year":2025,"claim":"Suggested AGO1 represses LIN28A transcription to control neural progenitor polarity through a downstream REELIN axis.","evidence":"AGO1 KO brain/organoids, LIN28A promoter ChIP and rescue (preprint)","pmids":["bio_10.1101_2025.10.01.679670"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Direct promoter binding mechanism not fully resolved"]},{"year":2025,"claim":"Linked nuclear AGO1 to paraspeckle biology via interaction with NEAT1 and paraspeckle proteins influencing chromatin compartments.","evidence":"Co-IP, co-localization and depletion experiments (preprint)","pmids":["bio_10.1101_2025.01.26.634929"],"confidence":"Low","gaps":["Co-IP and co-localization in a single unreviewed preprint","Direct vs indirect NEAT1 association not established"]},{"year":null,"claim":"How AGO1 mechanistically partitions among its cytoplasmic silencing, nuclear transcriptional, chromatin, and RNA-independent chaperone functions, and whether common recruitment determinants govern these states, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified structural model linking nuclear and chaperone functions","Determinants directing AGO1 to chromatin vs RISC not defined","Human in vivo validation of disease and chaperone roles incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[2,6,15,18]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[2,6,16]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[13,30,23]},{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[26]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3,13,20,25,30]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[9,18]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[17,22]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[25]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,2,6,16]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[13,23,30]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[25,23]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,30]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[26]}],"complexes":["RISC","paraspeckle"],"partners":["RNA POL II","NF-KB P65","HOP","HESO1","ROT3","GW182","14-3-3","NEAT1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UL18","full_name":"Protein argonaute-1","aliases":["Argonaute RISC catalytic component 1","Eukaryotic translation initiation factor 2C 1","eIF-2C 1","eIF2C 1","Putative RNA-binding protein Q99"],"length_aa":857,"mass_kda":97.2,"function":"Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs)","subcellular_location":"Cytoplasm, P-body","url":"https://www.uniprot.org/uniprotkb/Q9UL18/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/AGO1","classification":"Not Classified","n_dependent_lines":14,"n_total_lines":1208,"dependency_fraction":0.011589403973509934},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000092847","cell_line_id":"CID001212","localizations":[{"compartment":"cytoplasmic","grade":3}],"interactors":[{"gene":"TNRC6B","stoichiometry":10.0},{"gene":"TNRC6A","stoichiometry":4.0},{"gene":"TNRC6C","stoichiometry":4.0},{"gene":"AGO2","stoichiometry":4.0},{"gene":"FKBP5","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001212","total_profiled":1310},"omim":[{"mim_id":"620292","title":"NEURODEVELOPMENTAL DISORDER WITH LANGUAGE DELAY AND BEHAVIORAL ABNORMALITIES, WITH OR WITHOUT SEIZURES; NEDLBAS","url":"https://www.omim.org/entry/620292"},{"mim_id":"613146","title":"MICRO RNA 184; MIR184","url":"https://www.omim.org/entry/613146"},{"mim_id":"613004","title":"HUNTINGTIN; HTT","url":"https://www.omim.org/entry/613004"},{"mim_id":"612675","title":"SMALL CAJAL BODY-SPECIFIC RNA 15; SCARNA15","url":"https://www.omim.org/entry/612675"},{"mim_id":"611368","title":"MAELSTROM SPERMATOGENIC TRANSPOSON SILENCER; MAEL","url":"https://www.omim.org/entry/611368"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytoplasmic bodies","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/AGO1"},"hgnc":{"alias_symbol":["hAGO1"],"prev_symbol":["EIF2C1"]},"alphafold":{"accession":"Q9UL18","domains":[{"cath_id":"-","chopping":"43-222_364-402","consensus_level":"medium","plddt":91.4556,"start":43,"end":402},{"cath_id":"2.170.260.10","chopping":"226-345","consensus_level":"medium","plddt":92.6216,"start":226,"end":345},{"cath_id":"3.40.50.2300","chopping":"443-571","consensus_level":"high","plddt":96.5843,"start":443,"end":571},{"cath_id":"3.30.420.10","chopping":"574-816_836-845","consensus_level":"medium","plddt":94.6889,"start":574,"end":845}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UL18","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UL18-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UL18-F1-predicted_aligned_error_v6.png","plddt_mean":91.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=AGO1","jax_strain_url":"https://www.jax.org/strain/search?query=AGO1"},"sequence":{"accession":"Q9UL18","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UL18.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UL18/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UL18"}},"corpus_meta":[{"pmid":"11910010","id":"PMC_11910010","title":"Fertile hypomorphic ARGONAUTE (ago1) mutants impaired in post-transcriptional gene silencing and virus resistance.","date":"2002","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/11910010","citation_count":473,"is_preprint":false},{"pmid":"11016954","id":"PMC_11016954","title":"AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals.","date":"2000","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11016954","citation_count":388,"is_preprint":false},{"pmid":"16936728","id":"PMC_16936728","title":"Involvement of AGO1 and AGO2 in mammalian transcriptional silencing.","date":"2006","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16936728","citation_count":273,"is_preprint":false},{"pmid":"16600876","id":"PMC_16600876","title":"AGO1 homeostasis entails coexpression of MIR168 and AGO1 and preferential stabilization of miR168 by AGO1.","date":"2006","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/16600876","citation_count":253,"is_preprint":false},{"pmid":"12538514","id":"PMC_12538514","title":"Maelstrom, a Drosophila spindle-class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage.","date":"2003","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/12538514","citation_count":205,"is_preprint":false},{"pmid":"22858679","id":"PMC_22858679","title":"Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma.","date":"2012","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/22858679","citation_count":186,"is_preprint":false},{"pmid":"19066226","id":"PMC_19066226","title":"AGO1-miR173 complex initiates phased siRNA formation in plants.","date":"2008","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/19066226","citation_count":147,"is_preprint":false},{"pmid":"24086155","id":"PMC_24086155","title":"Ago1 Interacts with RNA polymerase II and binds to the promoters of actively transcribed genes in human cancer cells.","date":"2013","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24086155","citation_count":116,"is_preprint":false},{"pmid":"19763164","id":"PMC_19763164","title":"Redundant and specific roles of the ARGONAUTE proteins AGO1 and ZLL in development and small RNA-directed gene silencing.","date":"2009","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19763164","citation_count":96,"is_preprint":false},{"pmid":"24733911","id":"PMC_24733911","title":"Methylation protects microRNAs from an AGO1-associated activity that uridylates 5' RNA fragments generated by AGO1 cleavage.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24733911","citation_count":96,"is_preprint":false},{"pmid":"22361475","id":"PMC_22361475","title":"The Enamovirus P0 protein is a silencing suppressor which inhibits local and systemic RNA silencing through AGO1 degradation.","date":"2012","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/22361475","citation_count":95,"is_preprint":false},{"pmid":"15882589","id":"PMC_15882589","title":"The role of ARGONAUTE1 (AGO1) in meristem formation and identity.","date":"2005","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/15882589","citation_count":89,"is_preprint":false},{"pmid":"31628252","id":"PMC_31628252","title":"The viral F-box protein P0 induces an ER-derived autophagy degradation pathway for the clearance of membrane-bound AGO1.","date":"2019","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/31628252","citation_count":86,"is_preprint":false},{"pmid":"32393053","id":"PMC_32393053","title":"Suppression of Endothelial AGO1 Promotes Adipose Tissue Browning and Improves Metabolic Dysfunction.","date":"2020","source":"Circulation","url":"https://pubmed.ncbi.nlm.nih.gov/32393053","citation_count":56,"is_preprint":false},{"pmid":"32210269","id":"PMC_32210269","title":"Extracellular vesicles derived from human adipose-derived stem cells promote the exogenous angiogenesis of fat grafts via the let-7/AGO1/VEGF signalling pathway.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32210269","citation_count":55,"is_preprint":false},{"pmid":"35290117","id":"PMC_35290117","title":"A fungal effector suppresses the nuclear export of AGO1-miRNA complex to promote infection in plants.","date":"2022","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/35290117","citation_count":54,"is_preprint":false},{"pmid":"22174881","id":"PMC_22174881","title":"AGO1 and AGO2 act redundantly in miR408-mediated Plantacyanin regulation.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22174881","citation_count":51,"is_preprint":false},{"pmid":"20721975","id":"PMC_20721975","title":"Association of a common AGO1 variant with lung cancer risk: a two-stage case-control study.","date":"2010","source":"Molecular carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/20721975","citation_count":51,"is_preprint":false},{"pmid":"29848768","id":"PMC_29848768","title":"A Suppressor Screen for AGO1 Degradation by the Viral F-Box P0 Protein Uncovers a Role for AGO DUF1785 in sRNA Duplex Unwinding.","date":"2018","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/29848768","citation_count":40,"is_preprint":false},{"pmid":"14699070","id":"PMC_14699070","title":"ago1 and dcr1, two core components of the RNA interference pathway, functionally diverge from rdp1 in regulating cell cycle events in Schizosaccharomyces pombe.","date":"2003","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/14699070","citation_count":39,"is_preprint":false},{"pmid":"31392979","id":"PMC_31392979","title":"AGO-unbound cytosolic pool of mature miRNAs in plant cells reveals a novel regulatory step at AGO1 loading.","date":"2019","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31392979","citation_count":38,"is_preprint":false},{"pmid":"19706460","id":"PMC_19706460","title":"Immunopurification of Ago1 miRNPs selects for a distinct class of microRNA targets.","date":"2009","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/19706460","citation_count":38,"is_preprint":false},{"pmid":"10534406","id":"PMC_10534406","title":"Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence, genomic organization, localization to chromosomal bands 1p34-p35, and expression.","date":"1999","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/10534406","citation_count":37,"is_preprint":false},{"pmid":"32636339","id":"PMC_32636339","title":"The Intrinsically Disordered Protein CARP9 Bridges HYL1 to AGO1 in the Nucleus to Promote MicroRNA Activity.","date":"2020","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/32636339","citation_count":36,"is_preprint":false},{"pmid":"21813456","id":"PMC_21813456","title":"The miRNA pathway limits AGO1 availability during siRNA-mediated PTGS defense against exogenous RNA.","date":"2011","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/21813456","citation_count":33,"is_preprint":false},{"pmid":"31330067","id":"PMC_31330067","title":"Let-7a-regulated translational readthrough of mammalian AGO1 generates a microRNA pathway inhibitor.","date":"2019","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/31330067","citation_count":32,"is_preprint":false},{"pmid":"22318144","id":"PMC_22318144","title":"Enhanced susceptibility of Ago1/3 double-null mice to influenza A virus infection.","date":"2012","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/22318144","citation_count":32,"is_preprint":false},{"pmid":"33556337","id":"PMC_33556337","title":"A novel mechanism underlying alcohol dehydrogenase expression: hsa-miR-148a-3p promotes ADH4 expression via an AGO1-dependent manner in control and ethanol-exposed hepatic cells.","date":"2021","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/33556337","citation_count":31,"is_preprint":false},{"pmid":"19767612","id":"PMC_19767612","title":"Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 'Slicer' independent and can be mediated by Ago1.","date":"2009","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/19767612","citation_count":31,"is_preprint":false},{"pmid":"31786333","id":"PMC_31786333","title":"lncRNA PVT1 aggravates doxorubicin-induced cardiomyocyte apoptosis by targeting the miR-187-3p/AGO1 axis.","date":"2019","source":"Molecular and cellular probes","url":"https://pubmed.ncbi.nlm.nih.gov/31786333","citation_count":29,"is_preprint":false},{"pmid":"21846468","id":"PMC_21846468","title":"Ago1 and Ago2 differentially affect cell proliferation, motility and apoptosis when overexpressed in SH-SY5Y neuroblastoma cells.","date":"2011","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/21846468","citation_count":29,"is_preprint":false},{"pmid":"34288373","id":"PMC_34288373","title":"LncRNA PVT1 promotes the progression of ovarian cancer by activating TGF-β pathway via miR-148a-3p/AGO1 axis.","date":"2021","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34288373","citation_count":27,"is_preprint":false},{"pmid":"25591174","id":"PMC_25591174","title":"Pathogenesis of Soybean mosaic virus in soybean carrying Rsv1 gene is associated with miRNA and siRNA pathways, and breakdown of AGO1 homeostasis.","date":"2015","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/25591174","citation_count":26,"is_preprint":false},{"pmid":"25271087","id":"PMC_25271087","title":"Five children with deletions of 1p34.3 encompassing AGO1 and AGO3.","date":"2014","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/25271087","citation_count":26,"is_preprint":false},{"pmid":"33414440","id":"PMC_33414440","title":"MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1.","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/33414440","citation_count":25,"is_preprint":false},{"pmid":"24627180","id":"PMC_24627180","title":"Novel functional small RNAs are selectively loaded onto mammalian Ago1.","date":"2014","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/24627180","citation_count":23,"is_preprint":false},{"pmid":"34930816","id":"PMC_34930816","title":"De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability.","date":"2021","source":"Journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34930816","citation_count":22,"is_preprint":false},{"pmid":"34605025","id":"PMC_34605025","title":"Phytophthora infestans Ago1-associated miRNA promotes potato late blight disease.","date":"2021","source":"The New phytologist","url":"https://pubmed.ncbi.nlm.nih.gov/34605025","citation_count":22,"is_preprint":false},{"pmid":"27669275","id":"PMC_27669275","title":"Polymorphisms in GEMIN4 and AGO1 Genes Are Associated with the Risk of Lung Cancer: A Case-Control Study in Chinese Female Non-Smokers.","date":"2016","source":"International journal of environmental research and public health","url":"https://pubmed.ncbi.nlm.nih.gov/27669275","citation_count":22,"is_preprint":false},{"pmid":"35284630","id":"PMC_35284630","title":"Hsa_circ_0001666 promotes non-small cell lung cancer migration and invasion through miR-1184/miR-548I/AGO1 axis.","date":"2022","source":"Molecular therapy oncolytics","url":"https://pubmed.ncbi.nlm.nih.gov/35284630","citation_count":21,"is_preprint":false},{"pmid":"17043360","id":"PMC_17043360","title":"Interactions between the RNA interference effector protein Ago1 and 14-3-3 proteins: consequences for cell cycle progression.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17043360","citation_count":20,"is_preprint":false},{"pmid":"33832481","id":"PMC_33832481","title":"POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1.","date":"2021","source":"BMC pulmonary medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33832481","citation_count":17,"is_preprint":false},{"pmid":"34020507","id":"PMC_34020507","title":"Brassinosteroids inhibit miRNA-mediated translational repression by decreasing AGO1 on the endoplasmic reticulum.","date":"2021","source":"Journal of integrative plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/34020507","citation_count":17,"is_preprint":false},{"pmid":"38412125","id":"PMC_38412125","title":"Modeling neurodevelopmental disorder-associated human AGO1 mutations in Caenorhabditis elegans Argonaute alg-1.","date":"2024","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/38412125","citation_count":15,"is_preprint":false},{"pmid":"26872948","id":"PMC_26872948","title":"The Mechanistic Underpinnings of an ago1-Mediated, Environmentally Dependent, and Stochastic Phenotype.","date":"2016","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/26872948","citation_count":15,"is_preprint":false},{"pmid":"30213762","id":"PMC_30213762","title":"Further evidence of a causal association between AGO1, a critical regulator of microRNA formation, and intellectual disability/autism spectrum disorder.","date":"2018","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30213762","citation_count":15,"is_preprint":false},{"pmid":"34852230","id":"PMC_34852230","title":"Ago1 controls myogenic differentiation by regulating eRNA-mediated CBP-guided epigenome reprogramming.","date":"2021","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/34852230","citation_count":14,"is_preprint":false},{"pmid":"33037631","id":"PMC_33037631","title":"Targeted inactivation of the AGO1 homeologues of Nicotiana benthamiana reveals their distinct roles in development and antiviral defence.","date":"2020","source":"The New phytologist","url":"https://pubmed.ncbi.nlm.nih.gov/33037631","citation_count":14,"is_preprint":false},{"pmid":"36350638","id":"PMC_36350638","title":"tatDB: a database of Ago1-mediated targets of transfer RNA fragments.","date":"2023","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/36350638","citation_count":13,"is_preprint":false},{"pmid":"30284063","id":"PMC_30284063","title":"Droplet digital PCR using HER2/EIF2C1 ratio for detection of HER2 amplification in breast cancer tissues.","date":"2018","source":"Medical oncology (Northwood, London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/30284063","citation_count":13,"is_preprint":false},{"pmid":"27440184","id":"PMC_27440184","title":"Post-Translational Regulation of miRNA Pathway Components, AGO1 and HYL1, in Plants.","date":"2016","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/27440184","citation_count":12,"is_preprint":false},{"pmid":"31666609","id":"PMC_31666609","title":"Association study of AGO1 and AGO2 genes polymorphisms with recurrent pregnancy loss.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31666609","citation_count":12,"is_preprint":false},{"pmid":"26848539","id":"PMC_26848539","title":"Identification and functional characterization of the AGO1 ortholog in maize.","date":"2016","source":"Journal of integrative plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/26848539","citation_count":12,"is_preprint":false},{"pmid":"32470449","id":"PMC_32470449","title":"MiR-542-3p drives renal fibrosis by targeting AGO1 in vivo and in vitro.","date":"2020","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32470449","citation_count":12,"is_preprint":false},{"pmid":"28374846","id":"PMC_28374846","title":"Infections of virulent and avirulent viruses differentially influenced the expression of dicer-1, ago-1, and microRNAs in Bombus terrestris.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28374846","citation_count":11,"is_preprint":false},{"pmid":"36341350","id":"PMC_36341350","title":"Conformation-stabilizing ELISA and cell-based assays reveal patient subgroups targeting three different epitopes of AGO1 antibodies.","date":"2022","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36341350","citation_count":10,"is_preprint":false},{"pmid":"35236760","id":"PMC_35236760","title":"AGO1 regulates pericentromeric regions in mouse embryonic stem cells.","date":"2022","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/35236760","citation_count":10,"is_preprint":false},{"pmid":"37686018","id":"PMC_37686018","title":"GelMA Hydrogel as a Promising Delivery System for Osthole in the Treatment of Rheumatoid Arthritis: Targeting the miR-1224-3p/AGO1 Axis.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37686018","citation_count":10,"is_preprint":false},{"pmid":"19883398","id":"PMC_19883398","title":"The Kinesin motor protein Cut7 regulates biogenesis and function of Ago1-complexes.","date":"2010","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/19883398","citation_count":8,"is_preprint":false},{"pmid":"36945744","id":"PMC_36945744","title":"Small RNAs >26 nt in length associate with AGO1 and are upregulated by nutrient deprivation in the alga Chlamydomonas.","date":"2023","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/36945744","citation_count":8,"is_preprint":false},{"pmid":"32655817","id":"PMC_32655817","title":"AGO1 enhances the proliferation and invasion of cholangiocarcinoma via the EMT-associated TGF-β signaling pathway.","date":"2020","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/32655817","citation_count":7,"is_preprint":false},{"pmid":"36990227","id":"PMC_36990227","title":"LINC01116 modulates EMT process via binding with AGO1 mRNA in oesophageal squamous cell carcinoma.","date":"2023","source":"Biochimica et biophysica acta. Molecular cell research","url":"https://pubmed.ncbi.nlm.nih.gov/36990227","citation_count":7,"is_preprint":false},{"pmid":"32527935","id":"PMC_32527935","title":"Transcriptional repression of Myc underlies the tumour suppressor function of AGO1 in Drosophila.","date":"2020","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/32527935","citation_count":7,"is_preprint":false},{"pmid":"31724726","id":"PMC_31724726","title":"The association of AGO1 (rs595961G>A, rs636832A>G) and AGO2 (rs11996715C>A, rs2292779C>G, rs4961280C>A) polymorphisms and risk of recurrent implantation failure.","date":"2019","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/31724726","citation_count":7,"is_preprint":false},{"pmid":"33573197","id":"PMC_33573197","title":"Extensive Analysis of miRNA Trimming and Tailing Indicates that AGO1 Has a Complex Role in miRNA Turnover.","date":"2021","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/33573197","citation_count":6,"is_preprint":false},{"pmid":"40082396","id":"PMC_40082396","title":"HC-Pro inhibits HEN1 methyltransferase activity, leading to autophagic degradation of AGO1.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40082396","citation_count":5,"is_preprint":false},{"pmid":"34208898","id":"PMC_34208898","title":"Ago1 Affects the Virulence of the Fungal Plant Pathogen Zymoseptoria tritici.","date":"2021","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/34208898","citation_count":5,"is_preprint":false},{"pmid":"38458189","id":"PMC_38458189","title":"AGO1 controls protein folding in mouse embryonic stem cell fate decisions.","date":"2024","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/38458189","citation_count":4,"is_preprint":false},{"pmid":"40497425","id":"PMC_40497425","title":"RNAi of Ago1 and Ago2 Disrupts Molting in the White-Backed Planthopper (Sogatella furcifera).","date":"2025","source":"Archives of insect biochemistry and physiology","url":"https://pubmed.ncbi.nlm.nih.gov/40497425","citation_count":4,"is_preprint":false},{"pmid":"36563181","id":"PMC_36563181","title":"Complex congenital cardiovascular anomaly in a patient with AGO1-associated disorder.","date":"2022","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/36563181","citation_count":4,"is_preprint":false},{"pmid":"31916009","id":"PMC_31916009","title":"Dynamic distribution of ARGONAUTE1 (AGO1) and ARGONAUTE4 (AGO4) in Hyacinthus orientalis L. pollen grains and pollen tubes growing in vitro.","date":"2020","source":"Protoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/31916009","citation_count":3,"is_preprint":false},{"pmid":"40132882","id":"PMC_40132882","title":"Repression of AGO1 by AGO2 via let-7 microRNAs facilitates embryonic stem cell differentiation.","date":"2025","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/40132882","citation_count":2,"is_preprint":false},{"pmid":"37589173","id":"PMC_37589173","title":"A novel heterozygous truncating variant in the AGO1 gene in an Iranian family with schizophrenia as an unreported symptom.","date":"2023","source":"Annals of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37589173","citation_count":2,"is_preprint":false},{"pmid":"40654672","id":"PMC_40654672","title":"Endothelial AGO1 Drives Vascular Inflammation and Atherosclerosis via a Non-Canonical Nuclear Mechanism.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40654672","citation_count":1,"is_preprint":false},{"pmid":"40937387","id":"PMC_40937387","title":"Genetic Variants of AGO1*rs595961 and AGO2*rs4961280 with Susceptibility to Bladder Carcinoma.","date":"2024","source":"Indian journal of clinical biochemistry : IJCB","url":"https://pubmed.ncbi.nlm.nih.gov/40937387","citation_count":1,"is_preprint":false},{"pmid":"29030852","id":"PMC_29030852","title":"Genomic Tagging of AGO1 Using CRISPR/Cas9-Mediated Homologous Recombination.","date":"2018","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/29030852","citation_count":1,"is_preprint":false},{"pmid":"40346419","id":"PMC_40346419","title":"LncRNA PVT1 promotes proliferation and migration in gallbladder adenocarcinoma by modulating miR-2355-5p/AGO1 axis.","date":"2025","source":"In vitro cellular & developmental biology. Animal","url":"https://pubmed.ncbi.nlm.nih.gov/40346419","citation_count":1,"is_preprint":false},{"pmid":"33327713","id":"PMC_33327713","title":"Mixed-lineage leukemia protein modulates the loading of let-7a onto AGO1 by recruiting RAN.","date":"2021","source":"Haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/33327713","citation_count":1,"is_preprint":false},{"pmid":"39051182","id":"PMC_39051182","title":"DNA Hypomethylation Underlies Epigenetic Swapping between AGO1 and AGO1-V2 Isoforms in Tumors.","date":"2024","source":"Epigenomes","url":"https://pubmed.ncbi.nlm.nih.gov/39051182","citation_count":0,"is_preprint":false},{"pmid":"37066388","id":"PMC_37066388","title":"Modeling neurodevelopmental disorder-associated hAGO1 mutations in C. elegans Argonaute ALG-1.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/37066388","citation_count":0,"is_preprint":false},{"pmid":"41833722","id":"PMC_41833722","title":"Plasma EIF2C1 cell-free DNA as a novel biomarker for hepatocellular carcinoma diagnosis and risk stratification.","date":"2026","source":"Clinics and research in hepatology and gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/41833722","citation_count":0,"is_preprint":false},{"pmid":"39788736","id":"PMC_39788736","title":"rRFtargetDB: a database of Ago1-mediated targets of ribosomal RNA fragments.","date":"2025","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/39788736","citation_count":0,"is_preprint":false},{"pmid":"42213882","id":"PMC_42213882","title":"Dehydration-induced condensation of AGO1 modulates miRNA functionality.","date":"2026","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/42213882","citation_count":0,"is_preprint":false},{"pmid":"24199554","id":"PMC_24199554","title":"[Cloning and sequence analysis of AGO1 gene in Panax ginseng].","date":"2013","source":"Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica","url":"https://pubmed.ncbi.nlm.nih.gov/24199554","citation_count":0,"is_preprint":false},{"pmid":"42248458","id":"PMC_42248458","title":"Ago1 is required for the regulation of mitochondrial translation under heat stress in S. pombe.","date":"2026","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/42248458","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.01.679670","title":"AGO1 in neural progenitor cells orchestrates brain development and sociability via LIN28A-REELIN axis","date":"2025-10-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.01.679670","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.12.11.627053","title":"An endogenous cluster of target-directed microRNA degradation sites induces decay of distinct microRNA families","date":"2024-12-13","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.11.627053","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.10.16.682822","title":"The parasitic plant  <i>Cuscuta campestris</i>  selectively loads  <i>trans</i>  -species miRNAs onto host Argonautes, but not self Argonautes","date":"2025-10-16","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.16.682822","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.26.634929","title":"AGO1 interacts with  <i>NEAT1</i>  lncRNA and impacts nuclear compartments","date":"2025-01-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.26.634929","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.08.05.25333061","title":"Novel autoantibodies in patients with systemic sclerosis and gastrointestinal dysfunction provide insight into disease pathogenesis","date":"2025-08-07","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.05.25333061","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.05.28.656625","title":"Maternal control of RNA decay safeguards embryo development","date":"2025-06-01","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.28.656625","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.24.620027","title":"The Nuclear Pore Complex acts as a hub for pri-miRNA transcription and processing in plants","date":"2024-10-25","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.24.620027","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":44679,"output_tokens":8797,"usd":0.132996,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":18763,"output_tokens":7237,"usd":0.13737,"stage2_stop_reason":"end_turn"},"total_usd":0.270366,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"AGO1 (Arabidopsis ARGONAUTE1) is required for post-transcriptional gene silencing (PTGS/cosuppression); loss-of-function ago1 mutants are defective in PTGS, placing AGO1 as an essential component of the plant RNA silencing machinery. A single amino acid conserved in AGO1, QDE-2, and RDE-1 is essential for PTGS activity.\",\n      \"method\": \"Forward genetic screen; sequencing of ago1 mutants; PTGS reporter assays in Arabidopsis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function with defined molecular phenotype, replicated across multiple alleles, conserved residue identified\",\n      \"pmids\": [\"11016954\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Hypomorphic ago1 mutants in Arabidopsis are defective for PTGS and hypersensitive to virus infection, demonstrating that PTGS is more sensitive than development to AGO1 perturbation, and that AGO1-mediated PTGS functions as an antiviral defense mechanism.\",\n      \"method\": \"Genetic analysis of hypomorphic ago1 alleles; PTGS assays; virus infection assays\",\n      \"journal\": \"The Plant cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple hypomorphic alleles, orthogonal phenotypic readouts (PTGS efficiency and virus susceptibility), replicated genetic epistasis\",\n      \"pmids\": [\"11910010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Arabidopsis AGO1 encodes the RNA slicer enzyme of the miRNA pathway; AGO1-catalyzed mRNA cleavage of AGO1 mRNA is directed by miR168, and AGO1 preferentially stabilizes miR168 relative to other miRNAs, establishing an AGO1 homeostasis feedback loop. Disruption of any regulatory process disturbs miRNA pathway function.\",\n      \"method\": \"Genetic analysis of MIR168 and AGO1 mutants/transgenes; miRNA quantification; mRNA cleavage assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal genetic approaches, direct measurement of slicer activity and miRNA levels, clearly defined feedback mechanism\",\n      \"pmids\": [\"16600876\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Human AGO1 (hAGO1/EIF2C1) and AGO2 associate with gene promoter DNA in cells treated with antigene RNAs (agRNAs), mediating transcriptional silencing at promoters in the nucleus. Inhibiting AGO1 expression reverses both transcriptional and post-transcriptional silencing.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP); RNAi knockdown of AGO1/AGO2; gene expression assays in mammalian cells\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus knockdown rescue, single lab, two orthogonal methods\",\n      \"pmids\": [\"16936728\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The miR173-AGO1 complex in Arabidopsis has unique functionality required to initiate phased siRNA (tasiRNA) formation from TAS1 and TAS2 loci; a single miR173 target site is sufficient to route transcripts into the tasiRNA pathway, and this activity is distinct from other miRNA-AGO1 complexes.\",\n      \"method\": \"Genetic complementation with modified TAS loci; syn-tasiRNA reporter assays; co-immunoprecipitation of miR173-AGO1 complex\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reconstitution with modified loci, co-IP, single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"19066226\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"In Arabidopsis, ZLL (ZWILLE/PINHEAD/AGO10) negatively regulates AGO1 at the protein level (not mRNA level); loss of ZLL in ago1 hypomorphic mutants increases AGO1 protein. The PAZ domain of AGO1 (involved in small RNA binding) is interchangeable between AGO1 and ZLL, while the MID and PIWI domains (involved in 5'-end selectivity and mRNA cleavage) and the N-terminal domain confer functional specificity.\",\n      \"method\": \"Genetic double-mutant analysis; protein level quantification; domain-swap experiments between AGO1 and ZLL\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — domain swap experiments plus genetic epistasis, multiple alleles, two orthogonal methods in single lab\",\n      \"pmids\": [\"19763164\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Human AGO1 (EIF2C1) can mediate siRNA-directed mRNA degradation independently of AGO2 slicer activity; off-target and a portion of on-target siRNA-mediated mRNA degradation requires siRNA interaction with AGO1 or AGO2 and the RISC-loading complex but is independent of AGO2 cleavage.\",\n      \"method\": \"Antisense-mediated reduction of AGO proteins; AGO2 knockout cell lines; modified siRNAs; P-body protein depletion assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO cell lines plus antisense knockdown, multiple approaches, single lab\",\n      \"pmids\": [\"19767612\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"In fission yeast (S. pombe), Ago1 amino terminus binds 14-3-3 proteins; overexpression of the Ago1 N-terminus delays cell cycle at the G2/M boundary by inhibiting nuclear import of the mitosis-inducing phosphatase Cdc25, leading to constitutive phosphorylation of Cdc2 on tyrosine 15.\",\n      \"method\": \"Pulldown/co-immunoprecipitation of Ago1 with 14-3-3 proteins; overexpression of Ago1 N-terminus; Cdc25 localization assays; Cdc2 phosphorylation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus functional overexpression with defined biochemical readouts, single lab\",\n      \"pmids\": [\"17043360\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"S. pombe Ago1 (and Dcr1, but not Rdp1) is required for cell cycle checkpoint enactment (regulated Cdc2 hyperphosphorylation) upon genotoxic stress, cytokinesis, and mating, demonstrating functions independent of RNAi-mediated heterochromatin formation. Human AGO2 (hGERp95/EIF2C2/hAgo2) compensates for loss of ago1+ in fission yeast, suggesting conserved cell cycle functions.\",\n      \"method\": \"Null mutant analysis of ago1+, dcr1+, rdp1+ in S. pombe; epistasis; Cdc2 phosphorylation assays; complementation with human AGO2\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with null mutants, biochemical readout, cross-species complementation, single lab\",\n      \"pmids\": [\"14699070\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The kinesin motor Cut7 interacts with Ago1-containing RNPs in S. pombe and is required for biogenesis and/or stability of Ago1-containing cytoplasmic RNP complexes; Cut7 also interacts with Dcr1 and Rdp1 (Ago1 cognate binding proteins). Loss of Cut7 activity leads to increased centromeric transcripts consistent with PTGS defects.\",\n      \"method\": \"Genetic screen; pulldown and co-immunoprecipitation; microscopy of RNP complexes; centromeric transcript analysis\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP plus genetic screen and functional readout, single lab\",\n      \"pmids\": [\"19883398\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Arabidopsis AGO1 and AGO2 act redundantly in miR408-mediated regulation of Plantacyanin; neither single ago1 nor ago2 mutant abolishes this regulation, but the ago1 ago2 double mutant is compromised, showing overlapping specificity beyond the 5'-nucleotide rule.\",\n      \"method\": \"Genetic analysis of single and double ago1/ago2 mutants; miR408 target expression assays; complementation with 5'A and 5'U MIR408 transgenes\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with double mutants plus complementation, single lab\",\n      \"pmids\": [\"22174881\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The miRNA pathway limits AGO1 availability for siRNA-mediated PTGS defense against exogenous RNA in plants; plants supporting transgene PTGS exhibit increased AGO1 protein, and impairing miR168-directed regulation of AGO1 mRNA increases PTGS efficiency. Competition between siRNAs and miRNAs for AGO1 binding modulates PTGS efficiency.\",\n      \"method\": \"Transgene PTGS assays; AGO1 protein level quantification; genetic manipulation of miRNA pathway components; miR168-AGO1 mRNA interaction analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple genetic and molecular approaches, single lab, mechanistic model supported by protein quantification\",\n      \"pmids\": [\"21813456\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The viral F-box protein P0 (from enamovirus PEMV-1 and poleroviruses) destabilizes AGO1 through an F-box-like domain; this mechanism is conserved between phylogenetically unrelated viral suppressors, indicating AGO1 is a primary target of viral counter-silencing strategies.\",\n      \"method\": \"Transient silencing suppression assays; AGO1 protein level analysis in P0-expressing plants; F-box domain mutants\",\n      \"journal\": \"Virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional suppression assays plus domain mutants, single lab, two viral systems\",\n      \"pmids\": [\"22361475\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Human AGO1 (EIF2C1) directly interacts with RNA Polymerase II in the nucleus and associates with promoters of transcriptionally active genes genome-wide; nuclear AGO1 regulates expression of AGO1-bound genes implicated in oncogenic pathways including cell cycle progression.\",\n      \"method\": \"ChIP-seq; co-immunoprecipitation of AGO1 with RNA Pol II; biochemical fractionation; gene expression analysis\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ChIP-seq with biochemical co-IP, multiple orthogonal methods, genome-wide landscape in human cancer cells\",\n      \"pmids\": [\"24086155\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Arabidopsis AGO1 interacts with the miRNA nucleotidyl transferase HESO1 through its PAZ and PIWI domains; HESO1 can uridylate AGO1-bound miRNAs in vitro, and uridylation of 5' RNA fragments produced by miRNA-mediated cleavage is also AGO1-associated. Methylation by HEN1 protects miRNAs from this AGO1-associated HESO1 activity.\",\n      \"method\": \"Co-immunoprecipitation of AGO1-HESO1; in vitro uridylation assay with purified HESO1 and AGO1-bound miRNAs; genetic analysis of hen1 mutants\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of enzymatic activity, co-IP, genetic mutant analysis; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"24733911\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In mammals, novel small RNAs derived from tandem genomic loci associate exclusively with AGO1 but not AGO2, and their expression depends on AGO1 protein levels; knockdown of AGO1 dramatically reduces these AGO1-specific sRNAs, demonstrating that a sorting mechanism for the AGO1-4 family is functional in mammals.\",\n      \"method\": \"Immunoprecipitation followed by deep sequencing (IP-seq) of AGO1 and AGO2 from EBV-infected cells; AGO1 knockdown; target mRNA regulation assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal IP-seq plus knockdown validation, single lab\",\n      \"pmids\": [\"24627180\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"AGO1 contains a degron motif within its DUF1785 domain required for interaction with the SCF-P0 ubiquitin ligase complex and subsequent proteasomal degradation. A single point mutation in the DUF1785 domain (ago1-57) impairs RNA duplex unwinding of siRNA duplexes (but not miRNA duplexes), revealing that DUF1785 is required for RISC loading via siRNA strand separation, and is essential for phased siRNA production and sense transgene PTGS.\",\n      \"method\": \"Forward genetic suppressor screen; cell-free RISC reconstitution assay; in vitro RNA unwinding assay; site-directed mutagenesis; co-immunoprecipitation with SCF-P0\",\n      \"journal\": \"The Plant cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cell-free reconstitution, in vitro unwinding assay, mutagenesis, and co-IP in single lab with multiple orthogonal methods\",\n      \"pmids\": [\"29848768\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Arabidopsis AGO1 and P0 (viral suppressor of RNA silencing from TuYV) associate on the endoplasmic reticulum (ER); P0-mediated AGO1 degradation proceeds via an ATG5- and ATG7-dependent autophagic pathway, with ATI1 and ATI2 as ER-associated proteins that interact with both P0 and AGO1 and mediate loading into ER-associated vesicles transported to the vacuole.\",\n      \"method\": \"Co-immunoprecipitation; subcellular fractionation; confocal microscopy; ATG mutant analysis; ATI1/ATI2 interaction assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — co-IP, live imaging, genetic knockouts (atg5, atg7, ati1, ati2), multiple orthogonal approaches, single lab\",\n      \"pmids\": [\"31628252\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In Arabidopsis, a large pool of cytoplasmic mature miRNAs exists unbound to AGO1; miRNAs show highly different RISC-loading efficiencies determined by information in their precursors; AGO1 protein availability is a limiting factor for miRNA loading efficiency.\",\n      \"method\": \"Size-exclusion fractionation of cell extracts; high-throughput sequencing of small RNA pools; transient and transgenic expression of selected miRNAs; AGO1 overexpression\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — fractionation plus sequencing plus genetic manipulation, single lab\",\n      \"pmids\": [\"31392979\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Translational readthrough of human AGO1 mRNA, promoted by let-7a miRNA acting on a cis-sequence downstream of the canonical stop codon, generates a C-terminally extended isoform Ago1x. Ago1x can load miRNAs onto target mRNAs but lacks the ability to interact with GW182, preventing downstream silencing, so it functions as a competitive inhibitor of the canonical miRNA pathway.\",\n      \"method\": \"Reporter assays for translational readthrough; ribosome profiling data analysis; mass spectrometry; specific antibody detection; GW182 interaction assays; global translation measurement\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro and in vivo reporter assays, mass spectrometry, ribosome profiling, interaction assays, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"31330067\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CARP9, a nuclear-localized intrinsically disordered protein, bridges HYL1 to AGO1 in the nucleus to promote miRNA loading into AGO1. CARP9 interacts with HYL1 and AGO1 (but not other miRNA biogenesis factors), promotes HYL1-AGO1 interaction, stabilizes AGO1 and mature miRNAs, and deficiency in CARP9 results in reduced AGO1-loaded miRNAs and partial nuclear retention of miRNA.\",\n      \"method\": \"Co-immunoprecipitation of CARP9-HYL1 and CARP9-AGO1; miRNA loading assays; nuclear fractionation; genetic loss-of-function of CARP9\",\n      \"journal\": \"Plant physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, fractionation, genetic mutant analysis, single lab with multiple approaches\",\n      \"pmids\": [\"32636339\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In mouse endothelial cells, AGO1 (EIF2C1) suppresses thrombospondin-1 (THBS1/TSP1) via the miRNA pathway identified by CLIP-seq; endothelial-specific AGO1 deletion leads to inhibition of TSP1, increased vascularity, adipose tissue browning, improved insulin sensitivity, and metabolic benefits. TSP1 overexpression in AGO1-KO mice substantially attenuates these beneficial effects.\",\n      \"method\": \"EC-conditional AGO1 knockout mice; CLIP-seq (crosslinking immunoprecipitation-sequencing); metabolic phenotyping; TSP1 rescue experiments\",\n      \"journal\": \"Circulation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO in vivo with CLIP-seq, rescue experiments, multiple metabolic phenotypic readouts\",\n      \"pmids\": [\"32393053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Brassinosteroids (BRs) inhibit miRNA-mediated translational repression by reducing AGO1 localization at the endoplasmic reticulum (ER) in Arabidopsis; ROT3 (a BR biosynthesis enzyme) co-localizes with AGO1 at the ER and interacts with AGO1 in a GW motif-dependent manner; the AGO1-ROT3 interaction is necessary for ROT3 function.\",\n      \"method\": \"Subcellular fractionation; live cell imaging; co-immunoprecipitation of AGO1-ROT3; GW motif mutant analysis; BR treatment/mutant plants with translational repression readout\",\n      \"journal\": \"Journal of integrative plant biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, localization imaging, GW motif mutagenesis, single lab\",\n      \"pmids\": [\"34020507\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Human AGO1 (EIF2C1) controls skeletal muscle differentiation by regulating global H3K27 acetylation via modulation of the interaction between enhancer RNAs (eRNAs) and the CBP acetyltransferase, thereby enabling developmental enhancer activation. AGO1 depletion blocks CBP acetyltransferase activation and blocks the myogenic program including MyoD and downstream myogenic gene activation.\",\n      \"method\": \"AGO1 depletion (knockdown/KO) during myogenic differentiation; ChIP for H3K27ac; eRNA-CBP interaction assays; RNA-seq; ChIP-seq\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-seq, interaction assays, loss-of-function with defined molecular mechanism, single lab\",\n      \"pmids\": [\"34852230\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A secretory fungal effector VdSSR1 from Verticillium dahliae translocates to the plant nucleus and sequesters ALY family proteins (adaptors of the TREX complex) to interfere with nuclear export of the AGO1-miRNA complex, reducing cytoplasmic AGO1 and sRNA levels and thereby suppressing transkingdom antifungal RNAi.\",\n      \"method\": \"Co-immunoprecipitation of VdSSR1 with ALY proteins; AGO1 localization assays; sRNA quantification; virulence assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, protein localization, sRNA quantification, functional virulence readout, single lab\",\n      \"pmids\": [\"35290117\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"AGO1 regulates pericentromeric heterochromatin in mouse embryonic stem cells; AGO1 depletion causes redistribution of repressive histone mark H3K9me3 and HP1α away from pericentromeric regions, and major satellite transcripts are strongly upregulated in Ago1_KO mESCs. Specific miRNAs with complementarity to major satellites can partially regulate these transcripts.\",\n      \"method\": \"AGO1 knockout in mESCs; ChIP for H3K9me3 and HP1α; major satellite transcript quantification; AGO1 rescue experiments; Drosha KO comparison\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO with defined chromatin phenotype, rescue validation, single lab with multiple readouts\",\n      \"pmids\": [\"35236760\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In mouse embryonic stem cells (mESCs), AGO1 (EIF2C1) controls stemness independently of its RNA-binding activity through facilitating protein folding: AGO1 specifically interacts with HOP (a co-chaperone for HSP70/HSP90) and enhances folding of HOP client proteins with intrinsically disordered regions. This is an RNA-independent function divergent from AGO2's differentiation-promoting miRNA pathway function.\",\n      \"method\": \"AGO1 KO in mESCs; co-immunoprecipitation of AGO1 with HOP; protein folding assays; small RNA independence demonstrated by mutants; stem cell fate assays\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — co-IP, KO with defined cellular phenotype, RNA-independence demonstrated, novel mechanism, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"38458189\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"AGO2 represses AGO1 mRNA expression in mESCs via a conserved let-7 miRNA-binding site in the AGO1 3' UTR; mutation of this binding site at the endogenous locus abolishes AGO2-mediated repression of AGO1 mRNA and compromises exit from pluripotency, establishing a cross-regulatory mechanism between AGO1 and AGO2.\",\n      \"method\": \"Loss-of-function and gain-of-function approaches in mESCs; endogenous mutagenesis of let-7 binding site in AGO1 3' UTR; AGO1 mRNA quantification; pluripotency exit assays\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — endogenous site mutagenesis, gain/loss-of-function, functional pluripotency readout, single lab\",\n      \"pmids\": [\"40132882\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Human AGO1 NDD-associated mutations (modeled in C. elegans alg-1) cause antimorphic (dominant negative) effects on miRNA processing, miRISC formation, and target repression; mutant ALG-1 proteins likely sequester functional miRISC components into non-functional complexes. Allele-specific disruptions in mature miRNA profiles and downstream translational efficiency/mRNA abundance are observed.\",\n      \"method\": \"Knock-in of human AGO1 NDD mutations into C. elegans alg-1; miRNA profiling; translational efficiency measurement; gene expression analysis; dominant-negative epistasis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — precise knock-in genetics, multiple alleles, miRNA profiling, ribosome/translation readouts, cross-clade complementation approach\",\n      \"pmids\": [\"38412125\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"HC-Pro (viral suppressor from Turnip mosaic virus) inhibits HEN1 methyltransferase activity and recruits HEN1, ATG8a, and indirectly AGO1 into HC-Pro bodies (H-bodies), leading to autophagic degradation of AGO1 and accumulation of unmethylated miRNA duplexes and impairment of RISC assembly. Inhibition of HEN1 correlates with autophagic degradation of AGO1.\",\n      \"method\": \"FRET analysis of HC-Pro bodies; transgenic plant analysis; AGO1 protein level quantification; unMet-miRNA profiling; genetic analysis of hen1 and heso1 mutants\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FRET, transgenic analysis, genetic epistasis, single lab with multiple readouts\",\n      \"pmids\": [\"40082396\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Nuclear AGO1 (EIF2C1) in endothelial cells acts as a transcriptional coactivator of NF-κB by directly interacting with NF-κB p65, enhancing transcription of pro-inflammatory genes including ICAM1 and THBS1. EC-specific AGO1 deletion in mice reduces vascular inflammation, improves lipid metabolism, and attenuates atherosclerosis.\",\n      \"method\": \"EC-conditional AGO1 KO mice with atherosclerosis model; Cut&Tag sequencing; ChIP assays; co-IP of AGO1 with NF-κB p65; RNA-seq; monocyte adhesion assay; ASO-based therapeutic knockdown\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, ChIP/Cut&Tag, conditional KO in vivo with functional readouts; preprint, not peer-reviewed\",\n      \"pmids\": [\"40654672\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In mESCs, AGO1 is localized primarily in the nucleus of neural progenitor cells (NPCs) and binds the LIN28A promoter region to inhibit LIN28A transcription; AGO1 KO results in loss of NPC polarity via increased LIN28A, which reduces REELIN expression by binding REELIN mRNA; LIN28A knockdown or recombinant REELIN treatment rescues the polarity defect.\",\n      \"method\": \"AGO1 KO in mouse brain and human forebrain organoids; ChIP for AGO1 at LIN28A promoter; LIN28A-REELIN mRNA interaction assays; nuclear localization microscopy; LIN28A knockdown rescue\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP, KO organoid model, rescue experiments, multiple readouts; preprint, not peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.10.01.679670\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"AGO1 physically interacts with the lncRNA NEAT1 and key paraspeckle proteins (PSPs) in the nucleus and co-localizes with paraspeckles; AGO1 depletion disrupts both NEAT1 isoform expression, reduces PSP-NEAT1 interactions, and impairs paraspeckle formation. Conversely, NEAT1 depletion mis-localizes AGO1 from paraspeckles and alters active chromatin compartments.\",\n      \"method\": \"Co-immunoprecipitation of AGO1 with NEAT1 and PSPs; confocal microscopy co-localization; AGO1 and NEAT1 depletion experiments; nuclear fractionation\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-IP and co-localization in single preprint without peer review; preliminary mechanistic follow-up\",\n      \"pmids\": [\"bio_10.1101_2025.01.26.634929\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"The human EIF2C1 gene (AGO1) consists of 19 exons spanning ~50 kb, is located at chromosome 1p34-p35, is ubiquitously expressed at low-to-medium levels, and belongs to a multigene family sharing ~70% identity with plant AGO1, establishing it as a member of the conserved Argonaute family.\",\n      \"method\": \"cDNA cloning; genomic organization; chromosomal localization by fluorescence in situ hybridization; Northern blot expression analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cloning, FISH localization, expression analysis; foundational gene characterization paper\",\n      \"pmids\": [\"10534406\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Human AGO1 (EIF2C1/hAGO1) is a multi-functional Argonaute protein that serves as a core component of the RNA-induced silencing complex (RISC), associating with miRNAs and siRNAs to mediate post-transcriptional gene silencing via mRNA cleavage and translational repression; in the nucleus, it directly interacts with RNA Polymerase II and NF-κB p65 to regulate transcription of active genes and pro-inflammatory targets, maintains pericentromeric heterochromatin in embryonic stem cells, and controls cell fate (stemness) through an RNA-independent mechanism involving interaction with the HSP70/HSP90 co-chaperone HOP to facilitate protein folding of intrinsically disordered client proteins. AGO1 homeostasis is maintained by miR168-directed autoregulation and cross-regulation by AGO2 via let-7, while its levels are also controlled by viral suppressors (P0, HC-Pro) that target it for autophagic degradation through the endoplasmic reticulum, and by the DUF1785 domain which is required for siRNA duplex unwinding during RISC loading.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"AGO1 is a core Argonaute protein that binds small RNAs to direct post-transcriptional gene silencing, and which has acquired additional nuclear transcriptional and RNA-independent chaperone functions across eukaryotes [#0, #2, #13, #26]. In its canonical role it acts as the slicer enzyme of the miRNA pathway and an essential effector of antiviral PTGS, with siRNA-versus-miRNA competition and small-RNA sorting partitioning distinct substrate pools to AGO1 [#0, #1, #2, #15]. RISC loading requires the DUF1785 domain for siRNA duplex unwinding, while the MID and PIWI domains confer 5'-end selectivity and cleavage specificity, and human AGO1 can mediate siRNA-directed mRNA degradation independently of AGO2 slicer activity [#5, #6, #16]. AGO1 abundance is tightly homeostatic: it is autoregulated through miR168-directed cleavage of its own mRNA, cross-regulated by AGO2 via a let-7 site in its 3' UTR, and targeted for degradation by viral suppressors P0 (SCF-mediated) and HC-Pro through an ATG5/ATG7-dependent autophagic route at the endoplasmic reticulum [#2, #11, #16, #17, #27, #29]. In the nucleus, human AGO1 directly interacts with RNA Polymerase II at active promoters and acts as a transcriptional coactivator of NF-\\u03baB p65 to drive pro-inflammatory genes, and it maintains pericentromeric heterochromatin marked by H3K9me3 and HP1\\u03b1 in embryonic stem cells [#13, #25, #30]. Beyond RNA-based silencing, AGO1 controls stem cell fate independently of small-RNA binding by interacting with the HSP70/HSP90 co-chaperone HOP to promote folding of intrinsically disordered client proteins [#26]. In vivo, endothelial AGO1 suppresses thrombospondin-1 via the miRNA pathway, influencing vascular and metabolic phenotypes [#21]. Dominant-negative AGO1 mutations modeled in C. elegans disrupt miRISC formation and target repression, linking AGO1 to neurodevelopmental disorders [#28].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established AGO1 as an essential, genetically required component of the RNA silencing machinery, defining the biological process it serves before its molecular activity was known.\",\n      \"evidence\": \"Forward genetic screen and PTGS reporter assays in Arabidopsis ago1 mutants\",\n      \"pmids\": [\"11016954\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define AGO1's biochemical activity\", \"Conserved residue function not mechanistically resolved\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Showed AGO1-mediated PTGS functions as an antiviral defense and is more dose-sensitive than developmental roles, separating its silencing and developmental functions.\",\n      \"evidence\": \"Genetic analysis of hypomorphic ago1 alleles with PTGS and virus infection assays in Arabidopsis\",\n      \"pmids\": [\"11910010\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of antiviral specificity unresolved\", \"No direct biochemical activity assayed\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Identified AGO1 as the slicer enzyme of the miRNA pathway and uncovered miR168-directed autoregulation, providing the central homeostatic logic of AGO1 abundance.\",\n      \"evidence\": \"Genetic analysis of MIR168/AGO1, miRNA quantification, and mRNA cleavage assays in Arabidopsis\",\n      \"pmids\": [\"16600876\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of slicer catalysis not addressed\", \"Preferential miR168 stabilization mechanism unresolved\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrated human AGO1 functions in the nucleus at promoters to mediate transcriptional silencing, extending Argonaute function beyond cytoplasmic mRNA regulation.\",\n      \"evidence\": \"ChIP and RNAi knockdown with gene expression assays in mammalian cells\",\n      \"pmids\": [\"16936728\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Direct chromatin recruitment mechanism not defined\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Mapped domain-level functional specialization, assigning small-RNA binding to PAZ and cleavage/5'-selectivity to MID/PIWI, and revealed protein-level regulation of AGO1 by ZLL/AGO10.\",\n      \"evidence\": \"Genetic double-mutant analysis and domain-swap experiments between AGO1 and ZLL in Arabidopsis\",\n      \"pmids\": [\"19763164\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of ZLL-mediated protein regulation unresolved\", \"N-terminal domain specificity determinants not defined\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Showed human AGO1 can mediate siRNA-directed mRNA degradation independently of AGO2 slicer activity, establishing functional non-redundancy among human Argonautes.\",\n      \"evidence\": \"Antisense knockdown, AGO2 KO cell lines and modified siRNAs in human cells\",\n      \"pmids\": [\"19767612\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Degradation mechanism without slicing unresolved\", \"RISC-loading complex requirements only partially defined\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Revealed RNAi-independent cell-cycle functions of Ago1, linking its N-terminus to 14-3-3 binding, Cdc25 import, and checkpoint enactment under genotoxic stress.\",\n      \"evidence\": \"Co-IP, N-terminus overexpression, Cdc2 phosphorylation and checkpoint assays in S. pombe with human AGO2 complementation\",\n      \"pmids\": [\"17043360\", \"14699070\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between Ago1 and Cdc25 import indirect\", \"Relevance to mammalian AGO1 not tested\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified the kinesin Cut7 as required for biogenesis/stability of Ago1-containing cytoplasmic RNPs, connecting Ago1 effector complexes to cytoskeletal trafficking.\",\n      \"evidence\": \"Genetic screen, reciprocal co-IP, microscopy and centromeric transcript analysis in S. pombe\",\n      \"pmids\": [\"19883398\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect Cut7-Ago1 association unresolved\", \"Conservation in mammals untested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined AGO1-associated small-RNA quality control through HESO1-mediated uridylation of AGO1-bound miRNAs, counteracted by HEN1 methylation.\",\n      \"evidence\": \"Co-IP, in vitro uridylation reconstitution, and hen1 mutant analysis in Arabidopsis\",\n      \"pmids\": [\"24733911\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo turnover consequences of uridylation only partly defined\", \"Domain contacts for HESO1 binding not structurally mapped\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated active small-RNA sorting in mammals, with specific sRNA classes loaded exclusively into AGO1, reinforcing functional divergence among Argonautes.\",\n      \"evidence\": \"AGO1/AGO2 IP-seq and AGO1 knockdown in EBV-infected human cells\",\n      \"pmids\": [\"24627180\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Sorting determinants not defined\", \"Functional output of AGO1-specific sRNAs limited\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that nuclear human AGO1 directly binds RNA Pol II and associates with active promoters genome-wide, defining a transcriptional regulatory role at oncogenic gene programs.\",\n      \"evidence\": \"ChIP-seq, co-IP with RNA Pol II, and fractionation in human cancer cells\",\n      \"pmids\": [\"24086155\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of promoter selectivity unresolved\", \"Whether small RNAs guide nuclear AGO1 not settled\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Clarified that AGO1 abundance limits siRNA-versus-miRNA partitioning and PTGS efficiency, integrating miR168 autoregulation into antiviral defense capacity.\",\n      \"evidence\": \"Transgene PTGS assays with AGO1 protein quantification and miRNA-pathway manipulation in plants\",\n      \"pmids\": [\"21813456\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Quantitative competition parameters not defined\", \"Tissue-specific differences unaddressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Assigned the DUF1785 domain a dual role as a siRNA-unwinding module for RISC loading and a degron for SCF-P0-mediated degradation, mechanistically separating siRNA from miRNA duplex handling.\",\n      \"evidence\": \"Suppressor screen, cell-free RISC reconstitution, in vitro unwinding, mutagenesis and SCF-P0 co-IP in Arabidopsis\",\n      \"pmids\": [\"29848768\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of strand separation unresolved\", \"Why miRNA duplexes are exempt not fully explained\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined the route of viral P0-driven AGO1 turnover as ER-associated autophagy requiring ATG5/ATG7 and ATI1/ATI2, localizing AGO1 degradation to ER-derived vesicles.\",\n      \"evidence\": \"Co-IP, fractionation, confocal imaging and atg/ati mutant analysis in Arabidopsis\",\n      \"pmids\": [\"31628252\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trigger for ER recruitment unresolved\", \"Selectivity of autophagic cargo loading not fully defined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showed AGO1 protein availability limits miRNA loading and that a large unbound cytoplasmic miRNA pool exists, with precursor-encoded determinants of loading efficiency.\",\n      \"evidence\": \"Size-exclusion fractionation, small-RNA sequencing and AGO1 overexpression in Arabidopsis\",\n      \"pmids\": [\"31392979\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Precursor features dictating loading not enumerated\", \"Fate of unloaded miRNAs unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified a let-7-promoted readthrough isoform Ago1x that loads miRNAs but cannot recruit GW182, functioning as a competitive inhibitor of canonical silencing in humans.\",\n      \"evidence\": \"Readthrough reporters, ribosome profiling, mass spectrometry and GW182 interaction assays in human cells\",\n      \"pmids\": [\"31330067\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological abundance and contexts of Ago1x not fully mapped\", \"Regulation of readthrough beyond let-7 unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Showed nuclear miRNA loading into AGO1 is promoted by the disordered bridge protein CARP9 linking HYL1 to AGO1, defining a nuclear loading checkpoint in plants.\",\n      \"evidence\": \"Co-IP, nuclear fractionation, loading assays and CARP9 loss-of-function in Arabidopsis\",\n      \"pmids\": [\"32636339\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of bridging unresolved\", \"Conservation in animals untested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linked endothelial AGO1 to in vivo metabolic and vascular phenotypes through miRNA-mediated suppression of TSP1.\",\n      \"evidence\": \"EC-conditional AGO1 KO mice, CLIP-seq, metabolic phenotyping and TSP1 rescue\",\n      \"pmids\": [\"32393053\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct miRNA-target topology only inferred\", \"Tissue specificity of effect not fully dissected\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Connected BR signaling to miRNA activity by showing BRs reduce AGO1 ER localization through GW-motif-dependent ROT3 interaction, regulating translational repression.\",\n      \"evidence\": \"Fractionation, imaging, co-IP and GW-motif mutagenesis in Arabidopsis\",\n      \"pmids\": [\"34020507\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism coupling ER localization to repression unresolved\", \"Direct vs indirect ROT3 effects not separated\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Revealed a chromatin-level role for AGO1 in enabling enhancer activation via eRNA-CBP interaction and H3K27 acetylation during muscle differentiation.\",\n      \"evidence\": \"AGO1 loss-of-function, H3K27ac ChIP, eRNA-CBP assays and RNA/ChIP-seq in myogenic cells\",\n      \"pmids\": [\"34852230\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether small RNAs guide this function unresolved\", \"Direct AGO1-eRNA-CBP contacts not structurally defined\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed AGO1 maintains pericentromeric heterochromatin in mammalian stem cells, with depletion redistributing H3K9me3/HP1\\u03b1 and derepressing satellite transcripts.\",\n      \"evidence\": \"AGO1 KO in mESCs, H3K9me3/HP1\\u03b1 ChIP, satellite transcript quantification and rescue\",\n      \"pmids\": [\"35236760\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"miRNA dependence only partial\", \"Mechanism of HP1\\u03b1/H3K9me3 targeting unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined an RNA-independent function for AGO1 in stemness via interaction with the HOP co-chaperone to fold intrinsically disordered clients, diverging from AGO2's miRNA-based differentiation role.\",\n      \"evidence\": \"AGO1 KO in mESCs, AGO1-HOP co-IP, protein folding assays and RNA-independence mutants\",\n      \"pmids\": [\"38458189\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Client repertoire incompletely defined\", \"Structural basis of AGO1-HOP coupling unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established AGO2-to-AGO1 cross-regulation through a conserved let-7 site in the AGO1 3' UTR controlling exit from pluripotency.\",\n      \"evidence\": \"Endogenous let-7 site mutagenesis with gain/loss-of-function and pluripotency assays in mESCs\",\n      \"pmids\": [\"40132882\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Quantitative contribution to AGO1 dosage unresolved\", \"Conservation across lineages untested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected AGO1 to neurodevelopmental disease by showing patient mutations act dominant-negatively to sequester miRISC components and disrupt target repression.\",\n      \"evidence\": \"Knock-in of human AGO1 NDD mutations into C. elegans alg-1 with miRNA profiling and translation readouts\",\n      \"pmids\": [\"38412125\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism validated in invertebrate model\", \"Affected human neuronal pathways not directly mapped\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined nuclear AGO1 as an NF-\\u03baB p65 coactivator driving pro-inflammatory transcription and atherosclerosis in endothelium.\",\n      \"evidence\": \"EC-conditional AGO1 KO mice, Cut&Tag, ChIP, p65 co-IP and ASO knockdown (preprint)\",\n      \"pmids\": [\"40654672\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Direct vs indirect chromatin recruitment unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Suggested AGO1 represses LIN28A transcription to control neural progenitor polarity through a downstream REELIN axis.\",\n      \"evidence\": \"AGO1 KO brain/organoids, LIN28A promoter ChIP and rescue (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.10.01.679670\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Direct promoter binding mechanism not fully resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linked nuclear AGO1 to paraspeckle biology via interaction with NEAT1 and paraspeckle proteins influencing chromatin compartments.\",\n      \"evidence\": \"Co-IP, co-localization and depletion experiments (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.01.26.634929\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Co-IP and co-localization in a single unreviewed preprint\", \"Direct vs indirect NEAT1 association not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How AGO1 mechanistically partitions among its cytoplasmic silencing, nuclear transcriptional, chromatin, and RNA-independent chaperone functions, and whether common recruitment determinants govern these states, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified structural model linking nuclear and chaperone functions\", \"Determinants directing AGO1 to chromatin vs RISC not defined\", \"Human in vivo validation of disease and chaperone roles incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [2, 6, 15, 18]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [2, 6, 16]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [13, 30, 23]},\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [26]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3, 13, 20, 25, 30]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [9, 18]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [17, 22]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [25]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 2, 6, 16]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [13, 23, 30]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [25, 23]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 30]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [26]}\n    ],\n    \"complexes\": [\"RISC\", \"paraspeckle\"],\n    \"partners\": [\"RNA Pol II\", \"NF-kB p65\", \"HOP\", \"HESO1\", \"ROT3\", \"GW182\", \"14-3-3\", \"NEAT1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":8,"faith_total":8,"faith_pct":100.0}}