Affinage

AGO1

Protein argonaute-1 · UniProt Q9UL18

Length
857 aa
Mass
97.2 kDa
Annotated
2026-06-09
85 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 2000 High

    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

    PMID:11016954

    Open questions at the time
    • Did not define AGO1's biochemical activity
    • Conserved residue function not mechanistically resolved
  2. 2002 High

    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

    PMID:11910010

    Open questions at the time
    • Molecular basis of antiviral specificity unresolved
    • No direct biochemical activity assayed
  3. 2006 High

    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

    PMID:16600876

    Open questions at the time
    • Structural basis of slicer catalysis not addressed
    • Preferential miR168 stabilization mechanism unresolved
  4. 2006 Medium

    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

    PMID:16936728

    Open questions at the time
    • Single lab
    • Direct chromatin recruitment mechanism not defined
  5. 2009 High

    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

    PMID:19763164

    Open questions at the time
    • Mechanism of ZLL-mediated protein regulation unresolved
    • N-terminal domain specificity determinants not defined
  6. 2009 Medium

    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

    PMID:19767612

    Open questions at the time
    • Degradation mechanism without slicing unresolved
    • RISC-loading complex requirements only partially defined
  7. 2010 Medium

    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

    PMID:14699070 PMID:17043360

    Open questions at the time
    • Mechanistic link between Ago1 and Cdc25 import indirect
    • Relevance to mammalian AGO1 not tested
  8. 2010 Medium

    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

    PMID:19883398

    Open questions at the time
    • Direct vs indirect Cut7-Ago1 association unresolved
    • Conservation in mammals untested
  9. 2014 High

    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

    PMID:24733911

    Open questions at the time
    • In vivo turnover consequences of uridylation only partly defined
    • Domain contacts for HESO1 binding not structurally mapped
  10. 2014 Medium

    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

    PMID:24627180

    Open questions at the time
    • Sorting determinants not defined
    • Functional output of AGO1-specific sRNAs limited
  11. 2013 High

    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

    PMID:24086155

    Open questions at the time
    • Mechanism of promoter selectivity unresolved
    • Whether small RNAs guide nuclear AGO1 not settled
  12. 2016 Medium

    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

    PMID:21813456

    Open questions at the time
    • Quantitative competition parameters not defined
    • Tissue-specific differences unaddressed
  13. 2018 High

    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

    PMID:29848768

    Open questions at the time
    • Structural basis of strand separation unresolved
    • Why miRNA duplexes are exempt not fully explained
  14. 2019 High

    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

    PMID:31628252

    Open questions at the time
    • Trigger for ER recruitment unresolved
    • Selectivity of autophagic cargo loading not fully defined
  15. 2019 Medium

    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

    PMID:31392979

    Open questions at the time
    • Precursor features dictating loading not enumerated
    • Fate of unloaded miRNAs unresolved
  16. 2019 High

    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

    PMID:31330067

    Open questions at the time
    • Physiological abundance and contexts of Ago1x not fully mapped
    • Regulation of readthrough beyond let-7 unclear
  17. 2020 Medium

    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

    PMID:32636339

    Open questions at the time
    • Structural basis of bridging unresolved
    • Conservation in animals untested
  18. 2020 High

    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

    PMID:32393053

    Open questions at the time
    • Direct miRNA-target topology only inferred
    • Tissue specificity of effect not fully dissected
  19. 2021 Medium

    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

    PMID:34020507

    Open questions at the time
    • Mechanism coupling ER localization to repression unresolved
    • Direct vs indirect ROT3 effects not separated
  20. 2021 Medium

    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

    PMID:34852230

    Open questions at the time
    • Whether small RNAs guide this function unresolved
    • Direct AGO1-eRNA-CBP contacts not structurally defined
  21. 2022 Medium

    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

    PMID:35236760

    Open questions at the time
    • miRNA dependence only partial
    • Mechanism of HP1α/H3K9me3 targeting unresolved
  22. 2024 High

    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

    PMID:38458189

    Open questions at the time
    • Client repertoire incompletely defined
    • Structural basis of AGO1-HOP coupling unresolved
  23. 2024 Medium

    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

    PMID:40132882

    Open questions at the time
    • Quantitative contribution to AGO1 dosage unresolved
    • Conservation across lineages untested
  24. 2024 High

    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

    PMID:38412125

    Open questions at the time
    • Mechanism validated in invertebrate model
    • Affected human neuronal pathways not directly mapped
  25. 2025 Medium

    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)

    PMID:40654672

    Open questions at the time
    • Preprint, not peer-reviewed
    • Direct vs indirect chromatin recruitment unresolved
  26. 2025 Medium

    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)

    PMID:bio_10.1101_2025.10.01.679670

    Open questions at the time
    • Preprint, not peer-reviewed
    • Direct promoter binding mechanism not fully resolved
  27. 2025 Low

    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)

    PMID:bio_10.1101_2025.01.26.634929

    Open questions at the time
    • Co-IP and co-localization in a single unreviewed preprint
    • Direct vs indirect NEAT1 association not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0140110 transcription regulator activity 3 GO:0044183 protein folding chaperone 1
Localization
GO:0005634 nucleus 5 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2 R-HSA-392499 Metabolism of proteins 1
Partners
14-3-3GW182HESO1HOPNEAT1NF-KB P65RNA POL IIROT3
Complex memberships
RISCparaspeckle

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 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. Forward genetic screen; sequencing of ago1 mutants; PTGS reporter assays in Arabidopsis Proceedings of the National Academy of Sciences of the United States of America High 11016954
2002 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. Genetic analysis of hypomorphic ago1 alleles; PTGS assays; virus infection assays The Plant cell High 11910010
2006 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. Genetic analysis of MIR168 and AGO1 mutants/transgenes; miRNA quantification; mRNA cleavage assays Molecular cell High 16600876
2006 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. Chromatin immunoprecipitation (ChIP); RNAi knockdown of AGO1/AGO2; gene expression assays in mammalian cells Nature structural & molecular biology Medium 16936728
2008 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. Genetic complementation with modified TAS loci; syn-tasiRNA reporter assays; co-immunoprecipitation of miR173-AGO1 complex Proceedings of the National Academy of Sciences of the United States of America Medium 19066226
2009 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. Genetic double-mutant analysis; protein level quantification; domain-swap experiments between AGO1 and ZLL PLoS genetics High 19763164
2009 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. Antisense-mediated reduction of AGO proteins; AGO2 knockout cell lines; modified siRNAs; P-body protein depletion assays Nucleic acids research Medium 19767612
2010 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. Pulldown/co-immunoprecipitation of Ago1 with 14-3-3 proteins; overexpression of Ago1 N-terminus; Cdc25 localization assays; Cdc2 phosphorylation assays The Journal of biological chemistry Medium 17043360
2010 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. Null mutant analysis of ago1+, dcr1+, rdp1+ in S. pombe; epistasis; Cdc2 phosphorylation assays; complementation with human AGO2 Molecular biology of the cell Medium 14699070
2010 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. Genetic screen; pulldown and co-immunoprecipitation; microscopy of RNP complexes; centromeric transcript analysis Traffic (Copenhagen, Denmark) Medium 19883398
2011 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. Genetic analysis of single and double ago1/ago2 mutants; miR408 target expression assays; complementation with 5'A and 5'U MIR408 transgenes PloS one Medium 22174881
2011 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. Transgene PTGS assays; AGO1 protein level quantification; genetic manipulation of miRNA pathway components; miR168-AGO1 mRNA interaction analysis Nucleic acids research Medium 21813456
2012 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. Transient silencing suppression assays; AGO1 protein level analysis in P0-expressing plants; F-box domain mutants Virology Medium 22361475
2013 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. ChIP-seq; co-immunoprecipitation of AGO1 with RNA Pol II; biochemical fractionation; gene expression analysis PLoS genetics High 24086155
2014 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. Co-immunoprecipitation of AGO1-HESO1; in vitro uridylation assay with purified HESO1 and AGO1-bound miRNAs; genetic analysis of hen1 mutants Proceedings of the National Academy of Sciences of the United States of America High 24733911
2014 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. Immunoprecipitation followed by deep sequencing (IP-seq) of AGO1 and AGO2 from EBV-infected cells; AGO1 knockdown; target mRNA regulation assays Nucleic acids research Medium 24627180
2018 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. Forward genetic suppressor screen; cell-free RISC reconstitution assay; in vitro RNA unwinding assay; site-directed mutagenesis; co-immunoprecipitation with SCF-P0 The Plant cell High 29848768
2019 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. Co-immunoprecipitation; subcellular fractionation; confocal microscopy; ATG mutant analysis; ATI1/ATI2 interaction assays Proceedings of the National Academy of Sciences of the United States of America High 31628252
2019 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. Size-exclusion fractionation of cell extracts; high-throughput sequencing of small RNA pools; transient and transgenic expression of selected miRNAs; AGO1 overexpression Nucleic acids research Medium 31392979
2019 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. Reporter assays for translational readthrough; ribosome profiling data analysis; mass spectrometry; specific antibody detection; GW182 interaction assays; global translation measurement The EMBO journal High 31330067
2020 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. Co-immunoprecipitation of CARP9-HYL1 and CARP9-AGO1; miRNA loading assays; nuclear fractionation; genetic loss-of-function of CARP9 Plant physiology Medium 32636339
2020 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. EC-conditional AGO1 knockout mice; CLIP-seq (crosslinking immunoprecipitation-sequencing); metabolic phenotyping; TSP1 rescue experiments Circulation High 32393053
2020 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. Subcellular fractionation; live cell imaging; co-immunoprecipitation of AGO1-ROT3; GW motif mutant analysis; BR treatment/mutant plants with translational repression readout Journal of integrative plant biology Medium 34020507
2021 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. AGO1 depletion (knockdown/KO) during myogenic differentiation; ChIP for H3K27ac; eRNA-CBP interaction assays; RNA-seq; ChIP-seq Cell reports Medium 34852230
2021 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. Co-immunoprecipitation of VdSSR1 with ALY proteins; AGO1 localization assays; sRNA quantification; virulence assays Proceedings of the National Academy of Sciences of the United States of America Medium 35290117
2022 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. AGO1 knockout in mESCs; ChIP for H3K9me3 and HP1α; major satellite transcript quantification; AGO1 rescue experiments; Drosha KO comparison Life science alliance Medium 35236760
2024 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. AGO1 KO in mESCs; co-immunoprecipitation of AGO1 with HOP; protein folding assays; small RNA independence demonstrated by mutants; stem cell fate assays Developmental cell High 38458189
2024 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. 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 RNA (New York, N.Y.) Medium 40132882
2024 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. Knock-in of human AGO1 NDD mutations into C. elegans alg-1; miRNA profiling; translational efficiency measurement; gene expression analysis; dominant-negative epistasis Proceedings of the National Academy of Sciences of the United States of America High 38412125
2025 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. FRET analysis of HC-Pro bodies; transgenic plant analysis; AGO1 protein level quantification; unMet-miRNA profiling; genetic analysis of hen1 and heso1 mutants Nature communications Medium 40082396
2025 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. 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 bioRxivpreprint Medium 40654672
2025 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. 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 bioRxivpreprint Medium bio_10.1101_2025.10.01.679670
2025 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. Co-immunoprecipitation of AGO1 with NEAT1 and PSPs; confocal microscopy co-localization; AGO1 and NEAT1 depletion experiments; nuclear fractionation bioRxivpreprint Low bio_10.1101_2025.01.26.634929
1999 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. cDNA cloning; genomic organization; chromosomal localization by fluorescence in situ hybridization; Northern blot expression analysis Genomics Medium 10534406

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Fertile hypomorphic ARGONAUTE (ago1) mutants impaired in post-transcriptional gene silencing and virus resistance. The Plant cell 473 11910010
2000 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. Proceedings of the National Academy of Sciences of the United States of America 388 11016954
2006 Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nature structural & molecular biology 273 16936728
2006 AGO1 homeostasis entails coexpression of MIR168 and AGO1 and preferential stabilization of miR168 by AGO1. Molecular cell 253 16600876
2003 Maelstrom, a Drosophila spindle-class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage. Development (Cambridge, England) 205 12538514
2012 Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma. RNA biology 186 22858679
2008 AGO1-miR173 complex initiates phased siRNA formation in plants. Proceedings of the National Academy of Sciences of the United States of America 147 19066226
2013 Ago1 Interacts with RNA polymerase II and binds to the promoters of actively transcribed genes in human cancer cells. PLoS genetics 116 24086155
2014 Methylation protects microRNAs from an AGO1-associated activity that uridylates 5' RNA fragments generated by AGO1 cleavage. Proceedings of the National Academy of Sciences of the United States of America 96 24733911
2009 Redundant and specific roles of the ARGONAUTE proteins AGO1 and ZLL in development and small RNA-directed gene silencing. PLoS genetics 96 19763164
2012 The Enamovirus P0 protein is a silencing suppressor which inhibits local and systemic RNA silencing through AGO1 degradation. Virology 95 22361475
2005 The role of ARGONAUTE1 (AGO1) in meristem formation and identity. Developmental biology 89 15882589
2019 The viral F-box protein P0 induces an ER-derived autophagy degradation pathway for the clearance of membrane-bound AGO1. Proceedings of the National Academy of Sciences of the United States of America 86 31628252
2020 Suppression of Endothelial AGO1 Promotes Adipose Tissue Browning and Improves Metabolic Dysfunction. Circulation 56 32393053
2020 Extracellular vesicles derived from human adipose-derived stem cells promote the exogenous angiogenesis of fat grafts via the let-7/AGO1/VEGF signalling pathway. Scientific reports 55 32210269
2022 A fungal effector suppresses the nuclear export of AGO1-miRNA complex to promote infection in plants. Proceedings of the National Academy of Sciences of the United States of America 54 35290117
2011 AGO1 and AGO2 act redundantly in miR408-mediated Plantacyanin regulation. PloS one 51 22174881
2010 Association of a common AGO1 variant with lung cancer risk: a two-stage case-control study. Molecular carcinogenesis 51 20721975
2018 A Suppressor Screen for AGO1 Degradation by the Viral F-Box P0 Protein Uncovers a Role for AGO DUF1785 in sRNA Duplex Unwinding. The Plant cell 40 29848768
2003 ago1 and dcr1, two core components of the RNA interference pathway, functionally diverge from rdp1 in regulating cell cycle events in Schizosaccharomyces pombe. Molecular biology of the cell 39 14699070
2019 AGO-unbound cytosolic pool of mature miRNAs in plant cells reveals a novel regulatory step at AGO1 loading. Nucleic acids research 38 31392979
2009 Immunopurification of Ago1 miRNPs selects for a distinct class of microRNA targets. Proceedings of the National Academy of Sciences of the United States of America 38 19706460
1999 Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence, genomic organization, localization to chromosomal bands 1p34-p35, and expression. Genomics 37 10534406
2020 The Intrinsically Disordered Protein CARP9 Bridges HYL1 to AGO1 in the Nucleus to Promote MicroRNA Activity. Plant physiology 36 32636339
2011 The miRNA pathway limits AGO1 availability during siRNA-mediated PTGS defense against exogenous RNA. Nucleic acids research 33 21813456
2019 Let-7a-regulated translational readthrough of mammalian AGO1 generates a microRNA pathway inhibitor. The EMBO journal 32 31330067
2012 Enhanced susceptibility of Ago1/3 double-null mice to influenza A virus infection. Journal of virology 32 22318144
2021 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. Biochemical pharmacology 31 33556337
2009 Off-target and a portion of target-specific siRNA mediated mRNA degradation is Ago2 'Slicer' independent and can be mediated by Ago1. Nucleic acids research 31 19767612
2019 lncRNA PVT1 aggravates doxorubicin-induced cardiomyocyte apoptosis by targeting the miR-187-3p/AGO1 axis. Molecular and cellular probes 29 31786333
2011 Ago1 and Ago2 differentially affect cell proliferation, motility and apoptosis when overexpressed in SH-SY5Y neuroblastoma cells. FEBS letters 29 21846468
2021 LncRNA PVT1 promotes the progression of ovarian cancer by activating TGF-β pathway via miR-148a-3p/AGO1 axis. Journal of cellular and molecular medicine 27 34288373
2015 Pathogenesis of Soybean mosaic virus in soybean carrying Rsv1 gene is associated with miRNA and siRNA pathways, and breakdown of AGO1 homeostasis. Virology 26 25591174
2014 Five children with deletions of 1p34.3 encompassing AGO1 and AGO3. European journal of human genetics : EJHG 26 25271087
2021 MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1. Cell death & disease 25 33414440
2014 Novel functional small RNAs are selectively loaded onto mammalian Ago1. Nucleic acids research 23 24627180
2021 Phytophthora infestans Ago1-associated miRNA promotes potato late blight disease. The New phytologist 22 34605025
2021 De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability. Journal of medical genetics 22 34930816
2016 Polymorphisms in GEMIN4 and AGO1 Genes Are Associated with the Risk of Lung Cancer: A Case-Control Study in Chinese Female Non-Smokers. International journal of environmental research and public health 22 27669275
2022 Hsa_circ_0001666 promotes non-small cell lung cancer migration and invasion through miR-1184/miR-548I/AGO1 axis. Molecular therapy oncolytics 21 35284630
2006 Interactions between the RNA interference effector protein Ago1 and 14-3-3 proteins: consequences for cell cycle progression. The Journal of biological chemistry 20 17043360
2021 POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1. BMC pulmonary medicine 17 33832481
2021 Brassinosteroids inhibit miRNA-mediated translational repression by decreasing AGO1 on the endoplasmic reticulum. Journal of integrative plant biology 17 34020507
2024 Modeling neurodevelopmental disorder-associated human AGO1 mutations in Caenorhabditis elegans Argonaute alg-1. Proceedings of the National Academy of Sciences of the United States of America 15 38412125
2018 Further evidence of a causal association between AGO1, a critical regulator of microRNA formation, and intellectual disability/autism spectrum disorder. European journal of medical genetics 15 30213762
2016 The Mechanistic Underpinnings of an ago1-Mediated, Environmentally Dependent, and Stochastic Phenotype. Plant physiology 15 26872948
2021 Ago1 controls myogenic differentiation by regulating eRNA-mediated CBP-guided epigenome reprogramming. Cell reports 14 34852230
2020 Targeted inactivation of the AGO1 homeologues of Nicotiana benthamiana reveals their distinct roles in development and antiviral defence. The New phytologist 14 33037631
2023 tatDB: a database of Ago1-mediated targets of transfer RNA fragments. Nucleic acids research 13 36350638
2018 Droplet digital PCR using HER2/EIF2C1 ratio for detection of HER2 amplification in breast cancer tissues. Medical oncology (Northwood, London, England) 13 30284063
2020 MiR-542-3p drives renal fibrosis by targeting AGO1 in vivo and in vitro. Life sciences 12 32470449
2019 Association study of AGO1 and AGO2 genes polymorphisms with recurrent pregnancy loss. Scientific reports 12 31666609
2016 Identification and functional characterization of the AGO1 ortholog in maize. Journal of integrative plant biology 12 26848539
2016 Post-Translational Regulation of miRNA Pathway Components, AGO1 and HYL1, in Plants. Molecules and cells 12 27440184
2017 Infections of virulent and avirulent viruses differentially influenced the expression of dicer-1, ago-1, and microRNAs in Bombus terrestris. Scientific reports 11 28374846
2023 GelMA Hydrogel as a Promising Delivery System for Osthole in the Treatment of Rheumatoid Arthritis: Targeting the miR-1224-3p/AGO1 Axis. International journal of molecular sciences 10 37686018
2022 AGO1 regulates pericentromeric regions in mouse embryonic stem cells. Life science alliance 10 35236760
2022 Conformation-stabilizing ELISA and cell-based assays reveal patient subgroups targeting three different epitopes of AGO1 antibodies. Frontiers in immunology 10 36341350
2023 Small RNAs >26 nt in length associate with AGO1 and are upregulated by nutrient deprivation in the alga Chlamydomonas. The Plant cell 8 36945744
2010 The Kinesin motor protein Cut7 regulates biogenesis and function of Ago1-complexes. Traffic (Copenhagen, Denmark) 8 19883398
2023 LINC01116 modulates EMT process via binding with AGO1 mRNA in oesophageal squamous cell carcinoma. Biochimica et biophysica acta. Molecular cell research 7 36990227
2020 Transcriptional repression of Myc underlies the tumour suppressor function of AGO1 in Drosophila. Development (Cambridge, England) 7 32527935
2020 AGO1 enhances the proliferation and invasion of cholangiocarcinoma via the EMT-associated TGF-β signaling pathway. American journal of translational research 7 32655817
2019 The association of AGO1 (rs595961G>A, rs636832A>G) and AGO2 (rs11996715C>A, rs2292779C>G, rs4961280C>A) polymorphisms and risk of recurrent implantation failure. Bioscience reports 7 31724726
2021 Extensive Analysis of miRNA Trimming and Tailing Indicates that AGO1 Has a Complex Role in miRNA Turnover. Plants (Basel, Switzerland) 6 33573197
2025 HC-Pro inhibits HEN1 methyltransferase activity, leading to autophagic degradation of AGO1. Nature communications 5 40082396
2021 Ago1 Affects the Virulence of the Fungal Plant Pathogen Zymoseptoria tritici. Genes 5 34208898
2025 RNAi of Ago1 and Ago2 Disrupts Molting in the White-Backed Planthopper (Sogatella furcifera). Archives of insect biochemistry and physiology 4 40497425
2024 AGO1 controls protein folding in mouse embryonic stem cell fate decisions. Developmental cell 4 38458189
2022 Complex congenital cardiovascular anomaly in a patient with AGO1-associated disorder. American journal of medical genetics. Part A 4 36563181
2020 Dynamic distribution of ARGONAUTE1 (AGO1) and ARGONAUTE4 (AGO4) in Hyacinthus orientalis L. pollen grains and pollen tubes growing in vitro. Protoplasma 3 31916009
2025 Repression of AGO1 by AGO2 via let-7 microRNAs facilitates embryonic stem cell differentiation. RNA (New York, N.Y.) 2 40132882
2023 A novel heterozygous truncating variant in the AGO1 gene in an Iranian family with schizophrenia as an unreported symptom. Annals of human genetics 2 37589173
2025 LncRNA PVT1 promotes proliferation and migration in gallbladder adenocarcinoma by modulating miR-2355-5p/AGO1 axis. In vitro cellular & developmental biology. Animal 1 40346419
2025 Endothelial AGO1 Drives Vascular Inflammation and Atherosclerosis via a Non-Canonical Nuclear Mechanism. bioRxiv : the preprint server for biology 1 40654672
2024 Genetic Variants of AGO1*rs595961 and AGO2*rs4961280 with Susceptibility to Bladder Carcinoma. Indian journal of clinical biochemistry : IJCB 1 40937387
2021 Mixed-lineage leukemia protein modulates the loading of let-7a onto AGO1 by recruiting RAN. Haematologica 1 33327713
2018 Genomic Tagging of AGO1 Using CRISPR/Cas9-Mediated Homologous Recombination. Methods in molecular biology (Clifton, N.J.) 1 29030852
2026 Plasma EIF2C1 cell-free DNA as a novel biomarker for hepatocellular carcinoma diagnosis and risk stratification. Clinics and research in hepatology and gastroenterology 0 41833722
2026 Dehydration-induced condensation of AGO1 modulates miRNA functionality. The Plant cell 0 42213882
2026 Ago1 is required for the regulation of mitochondrial translation under heat stress in S. pombe. The Journal of biological chemistry 0 42248458
2025 rRFtargetDB: a database of Ago1-mediated targets of ribosomal RNA fragments. RNA (New York, N.Y.) 0 39788736
2024 DNA Hypomethylation Underlies Epigenetic Swapping between AGO1 and AGO1-V2 Isoforms in Tumors. Epigenomes 0 39051182
2023 Modeling neurodevelopmental disorder-associated hAGO1 mutations in C. elegans Argonaute ALG-1. bioRxiv : the preprint server for biology 0 37066388
2013 [Cloning and sequence analysis of AGO1 gene in Panax ginseng]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 0 24199554

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