Affinage

AGO2

Protein argonaute-2 · UniProt Q9UKV8

Length
859 aa
Mass
97.2 kDa
Annotated
2026-06-09
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AGO2 is the catalytic core of RNA-induced silencing, using loaded small RNAs to direct sequence-specific recognition and endonucleolytic slicing of target mRNAs, with quantitative target-binding and cleavage rules dictated by guide:target complementarity and tolerance for central-region insertions (PMID:31324449), and with the PAZ domain governing selective recognition of 3' nucleotides (PMID:24788663). Productive RISC assembly requires cytoplasmic chaperone-assisted loading: the Hsp90 cochaperones p23 and FKBP4 engage AGO2 prior to small-RNA loading (PMID:23741051), eIF1A binds the MID domain to promote RNAi and Dicer-independent miR-451 biogenesis (PMID:26018492), and autophagy via the receptor NDP52 selectively degrades miRNA-free AGO2 to sustain miRNA loading and homeostasis (PMID:23143396). AGO2 silencing activity is further tuned by post-translational modification and by RNA-binding cofactors that redirect target fate—p300/CBP acetylation and HDAC7 deacetylation control pre-miR-19b maturation (PMID:30305728), while FAM120A, MOV10/FMRP, Pumilio proteins, and Musashi-1 modulate or override miRNA-guided repression on subsets of transcripts (PMID:31289130, PMID:25464849, PMID:30333515, PMID:31903115), and YTHDF1 recruits AGO2 into phase-separated P-bodies for mRNA degradation (PMID:34821414). Beyond cytoplasmic silencing, AGO2 localization is dynamically partitioned by the PI3K-AKT-mTOR pathway: under low mTOR signaling it accumulates in the nucleus where its slicer activity represses young transposons co-transcriptionally (PMID:37985687), and it also participates in transcriptional gene silencing at promoters together with SETDB1 (PMID:16936728, PMID:25183519), saRNA-guided transcriptional activation through the RITA complex and RNA polymerase II (PMID:26902284), homologous-recombination repair by recruiting Rad51 to double-strand breaks (PMID:24662483), telomerase stimulation via TERT-TERC association (PMID:30591524), and mitochondrial translation activation of electron-transport-chain subunits through TUFM recruitment (PMID:38126189). KRAS-MEK signaling links AGO2 to oncogenic output by directly binding AGO2 at the ER and through S387 phosphorylation that controls AGO2 partitioning into multivesicular endosomes and exosomal miRNA export (PMID:26854235, PMID:27117408). AGO2 is essential for development, with knockout causing post-implantation embryonic lethality attributable to post-transcriptional rather than DNA-methylation defects (PMID:17418524), and heterozygous missense mutations that impair silencing or target release cause a neurological developmental disorder (PMID:33199684).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2006 Medium

    Established that AGO2 acts beyond cytoplasmic mRNA cleavage by associating with promoter DNA to mediate transcriptional gene silencing, raising the question of how a slicer functions in the nucleus.

    Evidence ChIP and AGO1/AGO2 knockdown rescue with synthetic agRNAs in cells

    PMID:16936728

    Open questions at the time
    • Did not define how AGO2 is recruited to chromatin
    • Did not establish the chromatin effectors downstream of promoter-bound AGO2
  2. 2007 High

    Determined that AGO2 is essential for early mammalian development and that its requirement is post-transcriptional, excluding a DNA-methylation maintenance role.

    Evidence Ago2 knockout mice with developmental phenotyping and bisulfite sequencing

    PMID:17418524

    Open questions at the time
    • Did not identify the specific miRNA targets driving lethality
    • Did not address tissue-specific functions masked by early lethality
  3. 2013 Medium

    Defined how RISC is assembled, showing Hsp90 cochaperones p23 and FKBP4 engage AGO2 before small-RNA loading in the cytoplasm.

    Evidence Reciprocal Co-IP, cochaperone knockdown, RISC loading assays, fractionation

    PMID:23741051

    Open questions at the time
    • Did not resolve the structural transitions during loading
    • Single-lab study without independent confirmation
  4. 2012 High

    Linked AGO2 turnover to miRNA homeostasis by showing miRNA-free AGO2 is cleared by NDP52-mediated selective autophagy, which is required for continued loading.

    Evidence Knockdown of NDP52/autophagy components, fractionation, miRNA activity assays

    PMID:23143396

    Open questions at the time
    • Did not define how NDP52 distinguishes loaded from unloaded AGO2
    • Did not quantify the kinetics of the loading/degradation cycle
  5. 2014 High

    Expanded AGO2's nuclear roles to genome maintenance and chromatin silencing, demonstrating Rad51 recruitment for HR repair and cooperation with SETDB1 for H3K9-methylation-based transcriptional silencing.

    Evidence Co-IP, ionizing radiation, catalytic mutants, HR/ChIP assays (two studies)

    PMID:24662483 PMID:25183519

    Open questions at the time
    • Did not identify the small RNAs guiding AGO2 to DSBs or promoters
    • Did not establish whether slicing of a target is required at break sites
  6. 2014 Medium

    Characterized PAZ-domain nucleotide selectivity, explaining selective 3'-end trimming and correlating binding strength with silencing efficacy.

    Evidence ITC binding assays with nucleotide analogues and in vivo silencing assays

    PMID:24788663

    Open questions at the time
    • No mutagenesis to confirm contact residues
    • Did not connect end recognition to RISC turnover in cells
  7. 2015 High

    Resolved direct cofactor control of catalysis by mapping eIF1A binding to the MID domain and showing it promotes RNAi and Dicer-independent miR-451 biogenesis.

    Evidence NMR, Co-IP, alanine mutagenesis, zebrafish rescue, RNAi assays

    PMID:26018492

    Open questions at the time
    • Did not define how eIF1A binding couples to slicing chemistry
    • Scope of eIF1A-dependent miRNAs not delineated
  8. 2015 Medium

    Showed that AGO2 nuclear versus cytoplasmic distribution is cell-type and tissue dependent, reframing its functional output as compartment-determined.

    Evidence Immunofluorescence, fractionation, tissue microarray IHC across tissues

    PMID:26699195

    Open questions at the time
    • Did not identify the signal driving tissue-specific nuclear localization
    • Correlative localization without functional consequence
  9. 2016 High

    Connected AGO2 to oncogenic KRAS signaling, showing direct ER binding to KRAS and MEK-driven S387 phosphorylation that governs exosomal miRNA export.

    Evidence Co-IP/MS, domain mapping, AGO2-/- cells, phospho-mutants, exosome isolation (two studies)

    PMID:26854235 PMID:27117408

    Open questions at the time
    • Did not establish how KRAS binding mechanistically attenuates silencing
    • Did not define the kinase acting directly on S387 versus pathway intermediates
  10. 2016 Medium

    Established AGO2 as a transcriptional activator through saRNA-guided assembly of the RITA complex with RNA polymerase II.

    Evidence Co-IP/MS, ChIP, RNA Pol II interaction assays

    PMID:26902284

    Open questions at the time
    • Did not resolve how saRNA selects activating versus silencing outcomes
    • Single-lab study without independent confirmation
  11. 2018 Medium

    Identified PTM and RNA-binding cofactors that tune AGO2 fate, including acetylation-controlled pre-miR-19b maturation and Pumilio antagonism/cooperation on shared 3'-UTRs.

    Evidence MS, K→R mutagenesis, Co-IP, CLIP-seq, reporter assays (two studies)

    PMID:30305728 PMID:30333515

    Open questions at the time
    • Mechanism of Pumilio-AGO2 allostery undefined
    • Did not establish in vivo relevance of individual acetylation sites
  12. 2018 High

    Revealed physiological consequences of AGO2 silencing in metabolism and extended its activity to non-canonical targets, with hepatic Ago2 suppressing metabolic genes and AGO2 stimulating telomerase via TERT-TERC.

    Evidence Liver-specific Ago2 knockout, metabolic phenotyping, miRNA profiling; telomerase and telomere-length assays (two studies)

    PMID:30201950 PMID:30591524

    Open questions at the time
    • Did not establish whether telomerase stimulation requires slicer activity
    • Did not connect metabolic and telomere roles mechanistically
  13. 2019 High

    Defined quantitative rules for RISC target recognition and cleavage and identified FAM120A as a cofactor that protects mRNAs from AGO2 degradation.

    Evidence High-throughput in vitro binding/cleavage with reconstituted RISC; IP-MS, iCLIP, reporter assays (two studies)

    PMID:31289130 PMID:31324449

    Open questions at the time
    • In vitro rules not exhaustively validated across endogenous transcriptomes
    • FAM120A protective mechanism at the RISC level unresolved
  14. 2020 High

    Linked AGO2 dysfunction to human disease by showing heterozygous missense mutations impair silencing or target release and cause a neurological developmental disorder.

    Evidence Patient fibroblasts, shRNA silencing assays, phosphorylation analysis, transcriptomics, P-body imaging

    PMID:33199684

    Open questions at the time
    • Did not establish the neuronal targets driving pathology
    • Did not define the kinase controlling the C-terminal serine cluster
  15. 2021 Medium

    Connected AGO2 to phase separation and translational control, showing YTHDF1 recruits AGO2 into liquid P-bodies for mRNA degradation and Trim71 represses AGO2 translation to control let-7 and stemness.

    Evidence Co-IP, FRAP, CRISPR KO, in vitro phase separation; polysome profiling and pluripotency assays (two studies)

    PMID:33599613 PMID:34821414

    Open questions at the time
    • Did not establish whether phase state is causal versus correlative for degradation
    • Single-lab studies for each mechanism
  16. 2023 High

    Resolved how mTOR signaling partitions AGO2 to the nucleus for slicer-dependent transposon repression and identified mitochondrial AGO2 activating ETC translation via TUFM.

    Evidence Fractionation, mTOR inhibition, catalytic mutants, ChIP/CLIP on transposons; mitochondrial Co-IP with TUFM, PTM analysis, AAV rescue (two studies)

    PMID:37985687 PMID:38126189

    Open questions at the time
    • Did not define the import machinery delivering AGO2 to mitochondria
    • Did not establish whether mitochondrial AGO2 uses small RNA guides
  17. 2024 Medium

    Demonstrated a compartment-specific pathological output, with nuclear AGO2 activating ANKRD1 transcription to drive cardiac dysfunction.

    Evidence AAV9 compartment-targeted AGO2, fractionation, TAC mouse model, chromatin assays, echocardiography

    PMID:38475992

    Open questions at the time
    • Did not define the guide RNA or mechanism of ANKRD1 promoter activation
    • Single-lab in vivo study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AGO2 is selectively trafficked among cytoplasm, nucleus, ER, multivesicular endosomes, and mitochondria, and how each localization couples to a distinct molecular activity, remains unresolved.
  • Import/export machinery for nuclear and mitochondrial AGO2 unknown
  • Whether non-cytoplasmic functions all require slicer activity and small-RNA guides is unresolved
  • Integration of PTM code (phosphorylation, acetylation, malonylation) with localization decisions is 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 4 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1 GO:0005768 endosome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-162582 Signal Transduction 2 R-HSA-73894 DNA Repair 1
Partners
EIF1AFAM120AKRASMOV10MSI1RAD51TUFMYTHDF1
Complex memberships
RISCRITA complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 AGO2 (and AGO1) associate with promoter DNA in cells treated with antigene RNAs (agRNAs) complementary to transcription start sites, mediating transcriptional gene silencing in the nucleus; inhibiting AGO1 or AGO2 expression reverses both transcriptional and post-transcriptional silencing. Chromatin immunoprecipitation, RNAi knockdown of AGO1/AGO2, synthetic agRNA transfection Nature structural & molecular biology Medium 16936728
2012 AGO2 (miRNA-free form) is targeted for selective autophagy-mediated degradation via the receptor NDP52; autophagy is required for continued miRNA loading onto AGO2 and for miRNA homeostasis. Genetic knockdown of NDP52/autophagy components, biochemical fractionation, functional miRNA activity assays Nature cell biology High 23143396
2014 AGO2 forms a complex with Rad51, and this interaction is enhanced by ionizing radiation; AGO2 catalytic activity and small RNA-binding capability are required for Rad51 accumulation at DSB sites and for homologous recombination repair. DSB resection and RPA/Mre11 loading are unaffected by AGO2 depletion. Co-immunoprecipitation, ionizing radiation treatment, AGO2 knockdown/catalytic mutants, HR repair assays Cell research High 24662483
2016 saRNA-loaded AGO2 guides assembly of the RNA-induced transcriptional activation (RITA) complex (containing AGO2, RHA, and CTR9/PAF1 complex component) at target promoters, interacting with RNA polymerase II to stimulate transcription initiation and elongation, accompanied by histone H2B monoubiquitination. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, RNA polymerase II interaction assays Cell research Medium 26902284
2016 KRAS-MEK signaling controls AGO2 localization to multivesicular endosomes (MVEs) and exosomal secretion; phosphorylation of AGO2 on serine 387 (downstream of MEK) prevents AGO2-MVE interactions and reduces AGO2 secretion into exosomes, thereby controlling miRNA levels in exosomes. Isogenic cell lines, MEK/Akt inhibitors, AGO2 phospho-mutant constructs, fractionation, exosome isolation Cell reports High 27117408
2016 KRAS directly binds AGO2 via its N-terminal domain interacting with the Switch II region of KRAS, independent of nucleotide (GDP/GTP) state; AGO2 and KRAS co-sediment and co-localize at the endoplasmic reticulum; oncogenic KRAS attenuates AGO2-mediated gene silencing and requires AGO2 for maximal mutant KRAS expression and cellular transformation. Co-immunoprecipitation mass spectrometry, subcellular fractionation, co-localization, AGO2-/- cells, domain interaction mapping Cell reports High 26854235
2014 SETDB1 (H3K9 methyltransferase) cooperates with AGO2 in agRNA-induced transcriptional gene silencing of the androgen receptor promoter; agRNA drives AGO2 recruitment to the promoter first, followed by SETDB1 recruitment; SETDB1 associates with SIN3-HDAC complex and EZH2, leading to trimethyl-H3K9 enrichment at the targeted promoter. DNA methylation is not significantly changed. Chromatin immunoprecipitation, knockdown of SETDB1/AGO2, co-immunoprecipitation, bisulfite sequencing Nucleic acids research Medium 25183519
2013 Hsp90 cochaperones p23 and FKBP4 physically interact with hAGO2 and are required for efficient RNAi; p23 and FKBP4 interact with hAGO2 before small RNA loading; RISC loading occurs in the cytoplasm rather than in RNA granules. Co-immunoprecipitation, RNAi knockdown of cochaperones, RISC loading assays, subcellular fractionation Molecular biology of the cell Medium 23741051
2014 MOV10 (RNA helicase) associates with FMRP and AGO2; MOV10 has a dual function—facilitating microRNA-mediated translation repression for some mRNAs and preventing AGO2 function on others; FMRP prevents MOV10-mediated microRNA suppression on a subset of mRNAs where FMRP and MOV10 bind in close proximity. Co-immunoprecipitation, RNA immunoprecipitation, iCLIP, AGO2 functional assays Cell reports Medium 25464849
2015 eIF1A directly interacts with the MID domain of AGO2 (confirmed by NMR and biochemical assays); this interaction promotes AGO2 activities in RNAi and Dicer-independent miR-451 biogenesis; alanine mutation of eIF1A Lys56 impairs RNAi in human cells and zebrafish. NMR, co-immunoprecipitation, alanine mutagenesis, zebrafish rescue experiments, RNAi activity assays Nature communications High 26018492
2015 Ago2 nuclear distribution is cell type- and tissue context-dependent; Ago2 localizes primarily as a nuclear protein in primary human keratinocytes and corresponding organotypic cultures, as well as in skin and cervical tissues, but not in continuous cell lines or larynx tissue. Immunofluorescence confocal microscopy, subcellular fractionation, tissue microarray immunohistochemistry The Journal of biological chemistry Medium 26699195
2018 AGO2 is acetylated by p300/CBP at K720, K493, and K355; deacetylation is performed by HDAC7; acetylation at K493/K720 (but not K355) specifically enhances pre-miR-19b1 recruitment to form the miRNA precursor deposit complex (miPDC) and promotes miR-19b maturation via recognition of the UGUGUG motif in the terminal loop of pre-miR-19b1. Mass spectrometry, site-directed mutagenesis (K→R), co-immunoprecipitation, AGO2 acetylation assays with p300/CBP and HDAC7 Oncogene Medium 30305728
2018 Hepatic Ago2-mediated RNA silencing regulates miRNAs (miR-802, miR-103/107, miR-148a/152) and suppresses metabolic genes (Hnf1β, Cav1, Ampka1); liver-specific Ago2 deletion enhances mitochondrial oxidation and ATP consumption linked to mRNA translation, causing AMPK activation and improving obesity-associated metabolic dysfunction. Liver-specific Ago2 knockout mice, metabolic phenotyping, miRNA profiling, AMPK activity assays Nature communications High 30201950
2018 AGO2 promotes telomerase activity and stimulates the association between TERT and TERC; AGO2 depletion results in shorter telomeres and reduced proliferation; AGO2 interacts with TERC and with a newly identified small RNA (terc-sRNA) arising from the H/ACA box of TERC; overexpression of terc-sRNA alone is sufficient to enhance telomerase activity. AGO2 gain- and loss-of-function, TERT/TERC interaction assays, telomere length measurement, RNA immunoprecipitation EMBO reports Medium 30591524
2019 FAM120A is an AGO2-interacting RNA-binding protein (identified by immunoprecipitation-MS) that binds poly(G) sequences in 3'-UTRs; FAM120A co-binding with AGO2 on target mRNAs prevents AGO2-mediated target degradation, sequestering miRNA-mediated repression. Co-immunoprecipitation mass spectrometry, iCLIP, luciferase reporter assays RNA (New York, N.Y.) Medium 31289130
2019 High-throughput SELEX/binding assays reveal quantitative rules for AGO2 RISC target binding and cleavage: RISC tolerates insertions up to 7 nt opposite the central guide region; specific guide:target mismatches can enhance cleavage rate; quantitative in vitro models predict knockdown in cellular systems. High-throughput in vitro binding assay (RBNS), single-turnover cleavage assays, mouse AGO2 RISC reconstitution Molecular cell High 31324449
2020 Thirteen heterozygous missense mutations in AGO2 found in patients with neurological developmental disorders each impair shRNA-mediated silencing; mechanistic consequences are either impaired RISC formation or increased AGO2-mRNA target binding associated with decreased phosphorylation of a C-terminal serine cluster involved in mRNA target release, increased dendritic P-body formation, and global transcriptome alterations. Patient-derived fibroblasts, shRNA silencing assays, AGO2 phosphorylation analysis, transcriptomics, P-body imaging Nature communications High 33199684
2020 Musashi-1 (MSI1) translocates to the cytoplasm under stress and forms a complex with AGO2; this MSI1/AGO2 complex stabilizes or destabilizes target mRNAs by binding to their 3'-UTR or coding sequence; disruption of the MSI1/AGO2 interaction (via C-terminal MSI1 overexpression) reduces stress-induced tumor progression. Co-immunoprecipitation, mass spectrometry, recombinant protein pulldown, RNA-IP, confocal microscopy, GBM xenograft Theranostics Medium 31903115
2021 YTHDF1 interacts with AGO2 via its YTH domain; YTHDF1 promotes P-body formation through liquid-liquid phase separation and recruits AGO2 for miRNA-mediated mRNA degradation; deletion of YTHDF1 causes P-bodies to convert from liquid to gel/solid AGO2/RNA patches, delaying mRNA degradation. Co-immunoprecipitation, immunofluorescence, 4SU-TT-seq, CRISPR knockout, FRAP, in vitro phase separation Cell proliferation Medium 34821414
2021 Trim71 represses AGO2 mRNA translation in mouse embryonic stem cells; blocking this repression leads to a post-transcriptional increase of mature let-7 miRNAs, resulting in let-7-dependent stemness defects and accelerated differentiation. Trim71 knockdown/overexpression, let-7 miRNA quantification, pluripotency assays, polysome profiling eLife Medium 33599613
2023 AGO2 in mitochondria of cardiomyocytes activates translation of electron transport chain subunits by recruiting TUFM (mitochondrial translation elongation factor); malonylation of AGO2 reduces its import into mitochondria in diabetic cardiomyopathy; this malonylation is regulated by a cytoplasmic short isoform of SIRT3 acting as a demalonylase. Mitochondrial fractionation, Co-IP of AGO2 with TUFM, adeno-associated virus delivery, post-translational modification analysis, echocardiography Circulation Medium 38126189
2023 In quiescent mouse splenocytes, AGO2 localizes almost exclusively to the nucleus; AGO2 nuclear accumulation is regulated by the Pi3K-AKT-mTOR pathway and is promoted when mTOR signaling is low (quiescence); in the nucleus, AGO2 binds young mobile transposons co-transcriptionally and represses their expression via its catalytic (slicer) domain. Subcellular fractionation, AGO2 localization imaging, mTOR pathway inhibition, AGO2 catalytic mutants, AGO2 ChIP/CLIP on transposons Nature structural & molecular biology High 37985687
2024 Nuclear AGO2 activates transcription of ANKRD1 (ankyrin repeat domain-containing protein 1) in failing hearts; nuclear (but not cytosolic) AGO2 overexpression exacerbates cardiac dysfunction; ANKRD1 nuclear import drives pathological MYH7 activation and cardiac remodeling; blocking ANKRD1 nuclear import (ivermectin or ANPep peptide) improves cardiac performance. AAV9-mediated AGO2 delivery, nuclear/cytosolic fractionation, TAC mouse model, chromatin assays, echocardiography Molecular therapy Medium 38475992
2017 AGO2 competes with IRF3 for binding to CBP/p300 in the nucleus; H5N1 viral infection reduces nuclear AGO2 distribution, relieving competition and promoting IRF3-CBP association and IFN-β transcription; AGO2 does not block IRF3 phosphorylation, nuclear translocation, or DNA binding. Co-immunoprecipitation, nuclear fractionation, H5N1 infection, IRF3-CBP interaction assays Frontiers in cellular and infection microbiology Medium 28589097
2014 The AGO2 PAZ domain selectively binds ribonucleotides (except adenosine) and poorly recognizes deoxyribonucleotides; the PAZ domain has an inherent lack of binding to adenine nucleotides, explaining selective trimming of 3'-adenylated miRNAs; stronger PAZ domain binders correlate with higher in vivo gene silencing efficacy. Biophysical binding assays (isothermal titration calorimetry), nucleotide analogue modifications, in vivo gene silencing assays PloS one Medium 24788663
2007 Disruption of Ago2 (Eif2c2) in mice causes embryonic lethality early in development after the implantation stage; Ago2 is not required for maintenance of DNA methylation at imprinted genes, centromeric repeats, or Xist, suggesting developmental defects are caused at the post-transcriptional (miRNA-protein complex) rather than transcriptional level. Ago2 gene knockout mice, bisulfite sequencing for DNA methylation, developmental phenotyping Genomics High 17418524
2018 Antagonistic and cooperative interactions between AGO2 and Pumilio proteins (PUM1/PUM2) on 3'-UTRs regulate mRNA targets; PUM binding near AGO2 sites can counteract miRNA-guided repression (antagonism) or cooperate to enhance AGO2 occupancy; this interaction is not explained by steric hindrance, suggesting an allosteric or indirect mechanism. CLIP-seq (transcriptome-wide AGO2 binding upon PUM knockdown), luciferase reporter assays Scientific reports Medium 30333515

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Biochemical functions of coenzyme Q10. Journal of the American College of Nutrition 615 11771674
2016 KRAS-MEK Signaling Controls Ago2 Sorting into Exosomes. Cell reports 362 27117408
2015 Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging cell 348 26111777
2007 Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Molecular biotechnology 298 17914161
2006 Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nature structural & molecular biology 273 16936728
2018 Coenzyme Q10 Supplementation in Aging and Disease. Frontiers in physiology 257 29459830
2018 Circular RNA circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes. Cell death and differentiation 250 30341421
2012 Selective autophagy degrades DICER and AGO2 and regulates miRNA activity. Nature cell biology 213 23143396
2014 Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination. Cell research 161 24662483
2010 High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2. Proceedings of the National Academy of Sciences of the United States of America 148 20385818
2014 Clinical applications of coenzyme Q10. Frontiers in bioscience (Landmark edition) 137 24389208
2020 Disorders of Human Coenzyme Q10 Metabolism: An Overview. International journal of molecular sciences 135 32933108
2007 Coenzyme Q10 and statins: biochemical and clinical implications. Mitochondrion 134 17482884
2019 High-Throughput Analysis Reveals Rules for Target RNA Binding and Cleavage by AGO2. Molecular cell 129 31324449
2001 Ubiquinone (coenzyme q10) and mitochondria in oxidative stress of parkinson's disease. Biological signals and receptors 124 11351130
2014 Coenzyme Q10 as a therapy for mitochondrial disease. The international journal of biochemistry & cell biology 123 24495877
2006 Human coenzyme Q10 deficiency. Neurochemical research 121 17094036
2007 One Argonaute family member, Eif2c2 (Ago2), is essential for development and appears not to be involved in DNA methylation. Genomics 120 17418524
2016 saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription. Cell research 116 26902284
2014 Coenzyme q10 therapy. Molecular syndromology 112 25126052
2018 Coenzyme Q10 deficiencies: pathways in yeast and humans. Essays in biochemistry 108 29980630
2004 Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the 'recoupling hypothesis'. QJM : monthly journal of the Association of Physicians 102 15256611
2014 MOV10 and FMRP regulate AGO2 association with microRNA recognition elements. Cell reports 94 25464849
2005 Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity. Integrative cancer therapies 94 15911925
2021 Metabolic Targets of Coenzyme Q10 in Mitochondria. Antioxidants (Basel, Switzerland) 92 33810539
2021 YTHDF1 promotes mRNA degradation via YTHDF1-AGO2 interaction and phase separation. Cell proliferation 83 34821414
2018 Clinical syndromes associated with Coenzyme Q10 deficiency. Essays in biochemistry 83 30030365
2009 Biosynthesis and bioproduction of coenzyme Q10 by yeasts and other organisms. Biotechnology and applied biochemistry 82 19531029
2020 Coenzyme Q10: Clinical Applications in Cardiovascular Diseases. Antioxidants (Basel, Switzerland) 78 32331285
2013 Co-enzyme Q10 and idebenone use in Friedreich's ataxia. Journal of neurochemistry 76 23859348
2015 miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively. Scientific reports 74 26507454
2007 Coenzyme Q10: a review of its promise as a neuroprotectant. CNS spectrums 73 17192765
2020 Germline AGO2 mutations impair RNA interference and human neurological development. Nature communications 70 33199684
2011 Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas. Virchows Archiv : an international journal of pathology 68 21769619
2021 Coenzyme Q10 supplementation - In ageing and disease. Mechanisms of ageing and development 60 34129891
2019 The Paradox of Coenzyme Q10 in Aging. Nutrients 60 31540029
2021 Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases. Nutrients 58 34067632
2021 Coenzyme Q10 and Cardiovascular Diseases. Antioxidants (Basel, Switzerland) 58 34205085
2020 AGO2 and its partners: a silencing complex, a chromatin modulator, and new features. Critical reviews in biochemistry and molecular biology 58 32164444
2021 Coenzyme Q10 and Immune Function: An Overview. Antioxidants (Basel, Switzerland) 57 34064686
2018 Acetylation of AGO2 promotes cancer progression by increasing oncogenic miR-19b biogenesis. Oncogene 56 30305728
2017 Cellular factories for coenzyme Q10 production. Microbial cell factories 54 28253886
2011 AGO1 and AGO2 act redundantly in miR408-mediated Plantacyanin regulation. PloS one 51 22174881
2019 LncRNA-CASC7 enhances corticosteroid sensitivity via inhibiting the PI3K/AKT signaling pathway by targeting miR-21 in severe asthma. Pulmonology 49 31412983
2018 Hydrogen sulfide upregulated lncRNA CasC7 to reduce neuronal cell apoptosis in spinal cord ischemia-reperfusion injury rat. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 45 29571256
2017 Therapeutic Potential of Co-enzyme Q10 in Retinal Diseases. Current medicinal chemistry 45 28762311
2008 Effects of ubiquinone (coenzyme Q10) on myopathy in statin users. Current opinion in lipidology 45 18957876
2020 miRNA-122-5p stimulates the proliferation and DNA synthesis and inhibits the early apoptosis of human spermatogonial stem cells by targeting CBL and competing with lncRNA CASC7. Aging 43 33231565
2002 Translocation der(13;21)(q10;q10) in skeletal and extraskeletal mesenchymal chondrosarcoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 43 12011263
1994 Coenzyme Q10, plasma membrane oxidase and growth control. Molecular aspects of medicine 43 7752819
2021 Coenzyme Q10 effects in neurological diseases. Physiological research 42 35199552
2014 AGO2 and SETDB1 cooperate in promoter-targeted transcriptional silencing of the androgen receptor gene. Nucleic acids research 42 25183519
2017 Biochemical Assessment of Coenzyme Q10 Deficiency. Journal of clinical medicine 40 28273876
2013 Strong reduction of AGO2 expression in melanoma and cellular consequences. British journal of cancer 40 24169347
2023 Primary Coenzyme Q10 Deficiency: An Update. Antioxidants (Basel, Switzerland) 39 37627647
2019 LncRNA CASC7 inhibits the progression of glioma via regulating Wnt/β-catenin signaling pathway. Pathology, research and practice 39 30661904
2017 Long non-coding RNA CASC7 inhibits the proliferation and migration of colon cancer cells via inhibiting microRNA-21. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 28954383
2016 KRAS Engages AGO2 to Enhance Cellular Transformation. Cell reports 38 26854235
2023 AGO2 Protects Against Diabetic Cardiomyopathy by Activating Mitochondrial Gene Translation. Circulation 36 38126189
2015 Cell Type- and Tissue Context-dependent Nuclear Distribution of Human Ago2. The Journal of biological chemistry 34 26699195
2005 Statins, cholesterol, Co-enzyme Q10, and Parkinson's disease. Parkinsonism & related disorders 34 15734664
2002 Human aging and global function of coenzyme Q10. Annals of the New York Academy of Sciences 34 11976213
2021 Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis. Cell death & disease 33 33846300
2018 Hepatic Ago2-mediated RNA silencing controls energy metabolism linked to AMPK activation and obesity-associated pathophysiology. Nature communications 33 30201950
2015 eIF1A augments Ago2-mediated Dicer-independent miRNA biogenesis and RNA interference. Nature communications 33 26018492
2013 Primary coenzyme Q10 (CoQ 10) deficiencies and related nephropathies. Pediatric nephrology (Berlin, Germany) 32 23736673
2024 tRF-33-P4R8YP9LON4VDP inhibits gastric cancer progression via modulating STAT3 signaling pathway in an AGO2-dependent manner. Oncogene 31 38783100
2019 Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer. BMC cancer 31 31324173
2013 Hsp90 cochaperones p23 and FKBP4 physically interact with hAgo2 and activate RNA interference-mediated silencing in mammalian cells. Molecular biology of the cell 31 23741051
2018 Antagonistic and cooperative AGO2-PUM interactions in regulating mRNAs. Scientific reports 29 30333515
2015 Expression of the microRNA regulators Drosha, Dicer and Ago2 in non-small cell lung carcinomas. Cellular oncology (Dordrecht, Netherlands) 29 26227789
2021 Repressing Ago2 mRNA translation by Trim71 maintains pluripotency through inhibiting let-7 microRNAs. eLife 28 33599613
2009 Coenzyme Q10 and alpha-tocopherol protect against amitriptyline toxicity. Toxicology and applied pharmacology 28 19263520
2022 Coenzyme Q10 in aging and disease. Critical reviews in food science and nutrition 27 36300654
2019 Sequestration of microRNA-mediated target repression by the Ago2-associated RNA-binding protein FAM120A. RNA (New York, N.Y.) 26 31289130
2017 AGO2 Negatively Regulates Type I Interferon Signaling Pathway by Competition Binding IRF3 with CBP/p300. Frontiers in cellular and infection microbiology 25 28589097
2023 AGO2 silences mobile transposons in the nucleus of quiescent cells. Nature structural & molecular biology 24 37985687
2019 Pristimerin inhibits glioma progression by targeting AGO2 and PTPN1 expression via miR-542-5p. Bioscience reports 23 31015365
2007 Coenzyme Q10 in phenylketonuria and mevalonic aciduria. Mitochondrion 23 17442628
2022 Coenzyme Q10 Supplement Rescues Postovulatory Oocyte Aging by Regulating SIRT4 Expression. Current molecular pharmacology 22 33881976
2021 Long non-coding RNA CASC7 suppresses malignant behaviors of breast cancer by regulating miR-21-5p/FASLG axis. Bioengineered 21 34889164
2017 AGO2 involves the malignant phenotypes and FAK/PI3K/AKT signaling pathway in hypopharyngeal-derived FaDu cells. Oncotarget 21 28903378
2014 Coenzyme Q10 increases cholesterol efflux and inhibits atherosclerosis through microRNAs. Arteriosclerosis, thrombosis, and vascular biology 21 25142877
2024 Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system. Acta biomaterialia 20 38561074
2018 AGO2 promotes telomerase activity and interaction between the telomerase components TERT and TERC. EMBO reports 20 30591524
2021 Neuroprotective effects of coenzyme Q10 in Parkinson's model via a novel Q10/miR-149-5p/MMPs pathway. Metabolic brain disease 19 34357552
2014 Bioenergetics and gene silencing approaches for unraveling nucleotide recognition by the human EIF2C2/Ago2 PAZ domain. PloS one 19 24788663
2022 Targeting coenzyme Q10 synthesis overcomes bortezomib resistance in multiple myeloma. Molecular omics 18 34879122
2021 An Aedes aegypti-Derived Ago2 Knockout Cell Line to Investigate Arbovirus Infections. Viruses 18 34205194
2020 Protective effects of Coenzyme Q10 against acute pancreatitis. International immunopharmacology 18 32829089
2020 Long non-coding RNA CASC7 is associated with the pathogenesis of heart failure via modulating the expression of miR-30c. Journal of cellular and molecular medicine 18 32860492
2017 Perinatal protein malnutrition alters expression of miRNA biogenesis genes Xpo5 and Ago2 in mice brain. Neuroscience letters 18 28300636
2020 Musashi-1 promotes stress-induced tumor progression through recruitment of AGO2. Theranostics 17 31903115
2023 Coenzyme Q10 Stimulate Reproductive Vatality. Drug design, development and therapy 16 37667786
2024 Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts. Molecular therapy : the journal of the American Society of Gene Therapy 15 38475992
2019 Multiple receptors converge on H2-Q10 to regulate NK and γδT-cell development. Immunology and cell biology 15 30537346
2015 IRF7 promotes glioma cell invasion by inhibiting AGO2 expression. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 25680411
2004 Coenzyme Q10 and lipid-related gene induction in HeLa cells. American journal of obstetrics and gynecology 15 15167860
2020 LncRNA cancer susceptibility candidate (CASC7) upregulates phosphatase and tensin homolog by downregulating miR-10a to inhibit neuroblastoma cell proliferation. Neuroreport 14 32101951
2019 The RNA-RNA base pairing potential of human Dicer and Ago2 proteins. Cellular and molecular life sciences : CMLS 14 31655860

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