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PRMT3

Protein arginine N-methyltransferase 3 · UniProt O60678

Length
531 aa
Mass
59.9 kDa
Annotated
2026-04-28
49 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRMT3 is a type I protein arginine methyltransferase that catalyzes asymmetric dimethylation of arginine residues in a distributive manner, functioning broadly in ribosome homeostasis, transcriptional regulation, innate immune signaling, and metabolic control. Its N-terminal C2H2 zinc-finger domain confers substrate specificity by tethering the enzyme to its primary physiological substrate, ribosomal protein S2 (rpS2/uS5), whose methylation regulates 40S:60S subunit balance, rpS2 stability via inhibition of ubiquitination, and activity-dependent translation in neurons (PMID:15175657, PMID:17439947, PMID:18573314, PMID:20647003). Beyond ribosome biology, PRMT3 methylates diverse non-ribosomal substrates — including RIG-I, MDA5, and cGAS to attenuate type I interferon responses; HIF1α and PDHK1 to reprogram glycolytic metabolism; HSP60 to maintain mitochondrial homeostasis; PCSK9 to block its ubiquitin-mediated degradation; and transcription factors TFAP2A and FOXO1 to alter their stability and nuclear localization — and deposits the H4R3me2a histone mark at target gene promoters, with nuclear translocation facilitated by ZNF200 and LXR⍺ (PMID:37639603, PMID:34753906, PMID:39256398, PMID:41797709, PMID:31378783, PMID:39513743, PMID:25187371). A potent allosteric inhibitor, SGC707, occupies a site distinct from the substrate and AdoMet pockets and blocks PRMT3 activity in vitro and in vivo (PMID:25728001).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    Establishing PRMT3 as a functional arginine methyltransferase capable of methylating protein substrates in vitro resolved the question of whether this newly identified PRMT family member had catalytic activity.

    Evidence In vitro methylation of PABP2/PABPN1 by recombinant PRMT3 with mass spectrometric site identification

    PMID:10224081

    Open questions at the time
    • No in vivo substrate validation
    • Physiological relevance of PABP2 methylation by PRMT3 versus PRMT1 unclear
  2. 2000 High

    Structural and biochemical characterization revealed the catalytic architecture and the role of the zinc-finger domain in substrate selectivity, distinguishing PRMT3 from other PRMTs.

    Evidence X-ray crystallography of PRMT3 catalytic core at 2.0 Å; zinc-finger deletion/mutation assays showing substrate specificity requirement

    PMID:10899106 PMID:10931850

    Open questions at the time
    • Structure of full-length PRMT3 with zinc-finger domain unresolved
    • No structural insight into zinc-finger–substrate recognition
  3. 2004 High

    Identification of rpS2/uS5 as the first physiological substrate of PRMT3 and the discovery of ribosomal subunit imbalance upon PRMT3 loss established a direct link between arginine methylation and ribosome homeostasis.

    Evidence TAP-MS in fission yeast; sucrose gradient co-sedimentation in yeast and human cells; PRMT3 genetic disruption showing 40S:60S imbalance

    PMID:15175657 PMID:15473865

    Open questions at the time
    • Whether ribosome imbalance causes translational defects was untested
    • Mechanism by which methylation affects subunit balance unknown
  4. 2004 High

    Discovery that the tumor suppressor DAL-1/4.1B binds the PRMT3 catalytic domain and inhibits its activity revealed the first endogenous negative regulator of PRMT3.

    Evidence Yeast two-hybrid, reciprocal Co-IP from cancer cell lines, and in vitro methylation inhibition assays

    PMID:15334060

    Open questions at the time
    • Physiological consequence of DAL-1 loss on PRMT3-dependent methylation in tumors not established
    • Structural basis of inhibition unknown
  5. 2007 High

    Knockout mouse studies confirmed rpS2 as a bona fide in vivo substrate that cannot be compensated by other PRMTs and revealed a Minute-like growth phenotype, grounding the ribosomal function in whole-animal physiology.

    Evidence PRMT3 targeted gene disruption in mice; rpS2 hypomethylation analysis; ribosome fractionation

    PMID:17439947

    Open questions at the time
    • PRMT3-null mice reach normal adult size, so compensatory mechanisms unclear
    • Additional ribosome-associated PRMT3 substrates remain unidentified
  6. 2008 Medium

    Demonstration that PRMT3 inhibits rpS2 ubiquitination and stabilizes it established a non-catalytic chaperone-like function of the zinc-finger domain in protecting substrates from proteasomal degradation.

    Evidence Domain deletion Co-IP; ubiquitination assays; rpS2 stability measurements upon PRMT3 overexpression

    PMID:18573314

    Open questions at the time
    • Whether methylation itself or merely binding inhibits ubiquitination not fully disentangled
    • E3 ligase targeting rpS2 not identified
  7. 2009 High

    Kinetic analysis established that PRMT3 catalyzes asymmetric dimethylation distributively, releasing monomethylated intermediates, resolving a fundamental question about the enzymatic mechanism of type I PRMTs.

    Evidence In vitro methylation kinetics with thin-layer chromatography of methylation products across multiple substrates

    PMID:19158082

    Open questions at the time
    • Whether distributive mechanism holds in a chromatin or ribosomal context in vivo untested
  8. 2010 Medium

    Linking PRMT3 to dendritic spine maturation and BDNF-induced translation established the first neuronal function for this enzyme, dependent on rpS2 methylation.

    Evidence siRNA knockdown in rat hippocampal neurons; methylation-resistant rpS2 mutant phenocopy

    PMID:20647003

    Open questions at the time
    • In vivo neuronal phenotype in PRMT3 KO mice not examined
    • Specific translational targets beyond αCaMKII not identified
  9. 2013 High

    Discovery and structural validation of an allosteric inhibition site on PRMT3, distinct from both substrate and cofactor pockets, opened a new avenue for selective pharmacological targeting of PRMTs.

    Evidence X-ray crystallography of PRMT3-inhibitor complex; non-competitive kinetic analysis

    PMID:23445220 PMID:25728001

    Open questions at the time
    • Whether allosteric inhibition affects all substrates equally unknown
    • Long-term in vivo toxicity of allosteric inhibitors not assessed
  10. 2014 Medium

    Discovery that PRMT3 binds LXRα in a methylation-independent manner and coactivates lipogenic transcription upon nuclear translocation revealed a non-enzymatic transcriptional coactivator function.

    Evidence Co-IP; nuclear fractionation upon palmitic acid treatment; PRMT3 KO MEFs; LXRα KO controls; reporter assays

    PMID:25187371

    Open questions at the time
    • Whether PRMT3 methylates LXRα targets' histones at lipogenic promoters not tested
    • Mechanism of fatty acid-induced nuclear import unknown
  11. 2018 Medium

    Identification of ZNF277 as a competitor for rpS2 binding via the same C2H2 zinc-finger recognition mode revealed a cotranslational regulatory circuit governing rpS2 partitioning between PRMT3-dependent methylation and other extraribosomal fates.

    Evidence Quantitative proteomics; reciprocal competition Co-IP upon PRMT3 overexpression/ZNF277 depletion

    PMID:30530495

    Open questions at the time
    • Functional consequence of ZNF277 vs. PRMT3 competition on ribosome assembly not established
    • Structural basis of shared zinc-finger recognition unknown
  12. 2019 Medium

    Demonstration that PRMT3 deposits H4R3me2a at specific promoters (miR-3648) to regulate osteogenic differentiation established PRMT3 as a bona fide histone-modifying enzyme with gene-specific transcriptional consequences.

    Evidence ChIP for H4R3me2a at miR-3648 promoter; miR-3648 rescue of PRMT3-deficient osteogenesis; in vivo osteopenia upon SGC707 treatment

    PMID:31378783

    Open questions at the time
    • Genome-wide H4R3me2a targets of PRMT3 not mapped
    • Whether H4R3me2a is the sole histone mark deposited by PRMT3 unclear
  13. 2023 High

    Identification of innate immune sensors RIG-I, MDA5, and cGAS as PRMT3 substrates whose nucleic acid-binding abilities are attenuated by asymmetric dimethylation established PRMT3 as a negative regulator of antiviral innate immunity.

    Evidence In vitro methylation with site-specific mutagenesis; RNA/DNA binding assays; Prmt3 haploinsufficient mice and SGC707 treatment during viral challenge

    PMID:37639603

    Open questions at the time
    • Whether PRMT3-mediated immune suppression is exploited by specific pathogens unknown
    • Upstream signals controlling PRMT3 activity during infection not identified
  14. 2023 Medium

    Expanding the substrate repertoire to metabolic and RNA-binding proteins (HIF1α, IGF2BP1, METTL14) linked PRMT3 to cancer metabolic reprogramming, drug resistance, and m6A epitranscriptomic regulation.

    Evidence Site-directed mutagenesis of HIF1α R282 and IGF2BP1 R452; HIF1α stability assays; CRISPR screen for oxaliplatin resistance; Co-IP of PRMT3-METTL14 with downstream m6A-seq

    PMID:34753906 PMID:37024475 PMID:37973560

    Open questions at the time
    • Direct methylation site on METTL14 not mapped
    • Whether HIF1α and IGF2BP1 methylation occur in normal physiology or only in cancer context unclear
  15. 2024 Medium

    Discovery of HSP60 and PDHK1 as PRMT3 substrates connected arginine methylation to mitochondrial protein homeostasis and metabolic immune evasion, showing that PRMT3 controls diverse organellar and signaling pathways.

    Evidence Site-directed mutagenesis of HSP60 R446 and PDHK1 R363/R368; mitochondrial integrity assays; PDHK1 kinase activity; ChIP for H3K18la at PD-L1; in vivo tumor models

    PMID:39256398 PMID:40050608

    Open questions at the time
    • Whether HSP60 oligomerization requires dimethylation versus monomethylation not distinguished
    • Relative contribution of PRMT3-PDHK1 axis versus direct HIF1α methylation to glycolytic reprogramming unknown
  16. 2024 Medium

    Identification of ZNF200 as a stabilizer of PRMT3 protein and facilitator of its nuclear import established a mechanism for regulated nuclear access and H4R3me2a deposition.

    Evidence Yeast two-hybrid, Co-IP, GST pull-down; proteasomal degradation assays; H4R3me2a western and ChIP upon ZNF200 manipulation

    PMID:39513743

    Open questions at the time
    • Signals controlling ZNF200-PRMT3 interaction unknown
    • Whether ZNF200 directs PRMT3 to specific genomic loci not tested
  17. 2025 Medium

    Expanding nuclear functions of PRMT3 to include HIV-1 latency reversal via H4R3me2a-dependent P-TEFb recruitment and transcription factor methylation (TFAP2A, FOXO1) solidified its role as a versatile transcriptional and epigenetic regulator beyond ribosome biology.

    Evidence dCas9-targeted locus-specific proteomics at HIV-1 LTR; Co-IP of PRMT3-P-TEFb-TEAD4; ChIP; TFAP2A methylation with stability/ChIP assays; FOXO1 R253 mutagenesis with decidualization and endometriosis models

    PMID:40374607 PMID:41129671 PMID:41455763

    Open questions at the time
    • Whether PRMT3 deposits H4R3me2a at endogenous human promoters genome-wide remains uncharacterized
    • Specificity determinants for PRMT3 recruitment to particular loci unknown
  18. 2026 High

    Demonstration that PRMT3 methylates PCSK9 at R582 to block CHIP-mediated ubiquitination and stabilize this procalcific factor established a methylation-ubiquitination crosstalk paradigm and linked PRMT3 to aortic valve calcification.

    Evidence IP-MS substrate identification; R582K and K575A mutagenesis; PCSK9 half-life assays; enzymatically dead PRMT3; Prmt3 haploinsufficient mice; SGC707 and PROTAC treatment

    PMID:41797709

    Open questions at the time
    • Whether the methylation-ubiquitination crosstalk mechanism generalizes to other PRMT3 substrates besides rpS2 and PCSK9 not systematically tested
  19. 2026 Medium

    Linking PRMT3 to insulin-pAKT-dependent feeding regulation and SLC25A1-mediated citrate transport in adipocytes connected PRMT3 to systemic metabolic physiology and diet-induced obesity.

    Evidence In vivo mouse models with diet-induced obesity and time-restricted feeding; SGC707 inhibition; adipocyte-specific Slc25a1 KO; ADMA proteomics

    PMID:41629293

    Open questions at the time
    • Direct methylation site on SLC25A1 not mapped
    • Whether PRMT3 acts on SLC25A1 transcription, protein stability, or both is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A comprehensive genome-wide map of PRMT3-deposited H4R3me2a sites, structural characterization of full-length PRMT3 with its zinc-finger domain bound to substrates, and systematic delineation of which substrates require enzymatic activity versus scaffolding remain major open questions.
  • No full-length PRMT3 structure with zinc-finger domain
  • No genome-wide ChIP-seq for PRMT3-dependent H4R3me2a in a defined cell type
  • Systematic distinction between catalytic and non-catalytic PRMT3 functions across substrates lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 6 GO:0042393 histone binding 4 GO:0140110 transcription regulator activity 4
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005840 ribosome 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1430728 Metabolism 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3
Partners
ALDH1A1DAL1LXRAMETTL14RPS2TEAD4ZNF200ZNF277

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Crystal structure of rat PRMT3 catalytic core in complex with AdoHcy revealed a two-domain architecture: an AdoMet-binding domain (compact version of consensus AdoMet-dependent methyltransferase fold) and a barrel-like domain, with the active site in a cone-shaped pocket between the two domains. The active site contains a double-E loop with two invariant Glu and a His-Asp proton-relay system conserved across the PRMT family. Crystal packing and solution behavior indicated dimer formation of the PRMT3 core. X-ray crystallography at 2.0 Å resolution; active-site residue analysis The EMBO journal High 10899106
1999 PRMT3 (along with PRMT1) methylates Poly(A)-binding protein II (PABP2/PABPN1) in vitro at Arg-Xaa-Arg clusters in its C-terminal domain, using S-adenosyl-L-methionine as methyl donor, demonstrating PABP2 as an in vitro substrate. In vitro methylation assay with recombinant PRMT1 and PRMT3; mass spectrometry and sequencing of methylated sites The Journal of biological chemistry High 10224081
2000 PRMT3 harbors a C2H2 zinc-finger domain in its N-terminus that is required for recognition of RNA-associated substrates in cell extracts but not for methylation of the artificial GST-GAR substrate. The zinc-finger domain confers substrate specificity. PRMT3 is inhibited by high ZnCl2 and N-ethylmaleimide (cysteine-modifying reagents), distinguishing it from PRMT1 and CARM1/PRMT4. In vitro methylation assays with zinc-finger deletion/mutation constructs; cell extract substrate assays; inhibitor sensitivity profiling The Journal of biological chemistry High 10931850
2004 PRMT3 ortholog in fission yeast associates with components of the translational machinery and methylates the 40S ribosomal protein S2 (rpS2/uS5) as its first identified physiological substrate. A fraction of yeast and human PRMT3 co-sediments with free 40S ribosomal subunits. Cells lacking PRMT3 show accumulation of free 60S ribosomal subunits, resulting in an imbalance in the 40S:60S free subunit ratio, without affecting pre-rRNA processing. Tandem affinity purification + mass spectrometry; sucrose gradient velocity centrifugation; genetic disruption of PRMT3 The EMBO journal High 15175657
2005 Mammalian rpS2 (ribosomal protein S2) is an in vivo substrate of PRMT3. The zinc-finger domain of PRMT3 is necessary and sufficient for binding to rpS2. PRMT3 methylates an N-terminal Arg-Gly repeat in rpS2 in vitro. Both PRMT3 and rpS2 co-sediment with free ribosomal subunits in mammalian cells. FLAG-tag pulldown from HeLa extracts; MS identification; in vitro methylation assay; deletion analysis; sucrose gradient co-sedimentation The Biochemical journal High 15473865
2004 DAL-1/4.1B tumor suppressor interacts with PRMT3 via the C-terminal catalytic core domain of PRMT3 (not the N-terminal zinc finger). DAL-1/4.1B is not a PRMT3 substrate but inhibits PRMT3-mediated methylation of GST-GAR in vitro and inhibits PRMT3 methylation of cellular substrates when expressed in MCF-7 cells. Yeast two-hybrid; co-immunoprecipitation from lung and breast cancer cell lines; in vitro binding assays; in vitro and cellular methylation assays Oncogene High 15334060
2007 In PRMT3 knockout mice, rpS2 is hypomethylated, confirming rpS2 as a bona fide in vivo PRMT3 substrate that cannot be compensated by other PRMTs. PRMT3-null mice are small at birth but reach normal adult size (Minute-like phenotype). Levels of 40S, 60S, and 80S monosomes and polyribosomes are unaffected by PRMT3 loss, but additional unidentified proteins co-fractionating with ribosomes are also dedicated PRMT3 substrates. Targeted gene disruption (knockout mice); ribosome fractionation; methylation analysis of rpS2 The Journal of biological chemistry High 17439947
2008 The rpS2 domain (residues 100–293, not the N-terminal RG repeat region) is required for binding to PRMT3, and this domain is susceptible to proteasomal degradation. The N-terminal region of PRMT3 (not the catalytic core) is required for binding to and stabilizing rpS2. PRMT3 overexpression inhibits ubiquitination of rpS2 and stabilizes it. Recombinant rpS2 in molar excess modestly increases PRMT3 enzymatic activity in vitro. Domain deletion analysis; co-immunoprecipitation; ubiquitination assay; in vitro enzymatic activity assay Biochimica et biophysica acta Medium 18573314
2009 PRMT3 (and PRMT1) catalyzes asymmetric dimethylation of arginine in a distributive manner: the two methyl groups are transferred to a single arginine with intermittent release of the monomethylated intermediate (not processively). This distributive mechanism holds even for substrates with multiple methyl-accepting arginines (up to 13 residues). In vitro methylation kinetics assays; thin-layer chromatography of methylation products; multiple substrate analysis The Journal of biological chemistry High 19158082
2010 PRMT3 is essential for dendritic spine maturation in rat hippocampal neurons. PRMT3 knockdown caused deformed spines, reduced BDNF-induced translation of αCaMKII, and diminished rpS2 protein stability. Overexpression of methylation-resistant rpS2 (with RG repeat deletions) phenocopied PRMT3 knockdown, linking the neuronal function of PRMT3 to rpS2 methylation-dependent translational regulation. siRNA knockdown in cultured rat hippocampal neurons; morphological analysis of dendritic spines; overexpression of methylation-resistant rpS2 mutant Brain research Medium 20647003
2010 Tyrosine 87 of human PRMT3 is critical for interaction with RPS2 and for full enzymatic activity. Tyr87Cys and Tyr87Glu (phosphomimetic) substitutions markedly decreased affinity for RPS2 and reduced methyltransferase activity, while Tyr87Phe (non-phosphorylatable) was unaffected. Serines 25 and 27 of PRMT3 were found to be phosphorylated by mass spectrometry. Site-directed mutagenesis; in vitro binding assays; enzymatic activity assays; mass spectrometry for phosphorylation sites Biochimica et biophysica acta Medium 21059412
2013 PRMT3 possesses an allosteric binding site distinct from the substrate and AdoMet binding sites. Compounds occupying this allosteric site inhibit PRMT3 non-competitively with both peptide substrate and cofactor. X-ray crystal structure of a compound bound to the allosteric site confirmed this inhibition mechanism. X-ray crystallography of PRMT3-inhibitor complex; enzyme kinetics (competitive inhibition analysis); structure-activity relationship studies Journal of medicinal chemistry High 23445220
2014 PRMT3 directly binds LXRα in a methylation-independent manner and acts as a transcriptional coactivator of LXRα to enhance lipogenic gene expression. Palmitic acid treatment translocates PRMT3 to the nucleus. PRMT3 overexpression increases lipogenic proteins while PRMT3 silencing decreases them. PRMT3-LXRα interaction is increased by high-fat diet and in NAFLD. Co-immunoprecipitation; PRMT3 overexpression/silencing; PRMT3 KO MEFs; nuclear fractionation showing translocation; LXRα KO mice as control; reporter assays Diabetes Medium 25187371
2015 SGC707 is a potent (IC50=31 nM, KD=53 nM), selective allosteric inhibitor of PRMT3 that engages PRMT3 and inhibits its methyltransferase activity in cells. Crystal structure of the PRMT3-SGC707 complex confirms allosteric inhibition mode. SGC707 is bioavailable and suitable for in vivo studies. Crystal structure of PRMT3-SGC707 complex; biochemical IC50/KD measurements; cellular target engagement assays; selectivity panel against 31 methyltransferases Angewandte Chemie (International ed. in English) High 25728001
2018 ZNF277 is a new extraribosomal binding partner of uS5 (RPS2) in human cells. ZNF277 uses a C2H2-type zinc finger domain (same as PRMT3) to recognize uS5. ZNF277 and PRMT3 compete for uS5 binding: PRMT3 overexpression inhibits ZNF277-uS5 complex formation, and ZNF277 depletion increases uS5-PRMT3 levels. ZNF277 recognizes nascent uS5 cotranslationally. Quantitative proteomics; co-immunoprecipitation; competition assays with PRMT3 overexpression/ZNF277 depletion; live cell imaging for localization The Journal of biological chemistry Medium 30530495
2019 PRMT3 promotes osteogenic differentiation of human mesenchymal stem cells by enhancing histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) at the promoter of miR-3648, thereby activating miR-3648 expression. Overexpression of miR-3648 rescues impaired osteogenesis in PRMT3-deficient cells. SGC707 or Prmt3 shRNA causes an osteopenia phenotype in mice. PRMT3 knockdown/overexpression; ChIP for H4R3me2a; miR-3648 rescue experiments; in vivo mouse model with shRNA or SGC707 Cell death & disease Medium 31378783
2021 PRMT3 interacts with ALDH1A1 (retinal dehydrogenase 1) via its catalytic domain, and this interaction inhibits ALDH1A1 enzymatic activity, negatively regulating expression of retinoic acid-responsive genes in a methyltransferase activity-independent manner. Specific residues in the PRMT3 catalytic domain mediating the interaction were identified by molecular docking and site-directed mutagenesis. Yeast two-hybrid; co-immunoprecipitation; in vitro pull-down; ALDH1A1 enzymatic activity assays; site-directed mutagenesis; gene expression analysis Communications biology Medium 33495566
2023 PRMT3 methylates IGF2BP1 at R452, which stabilizes HEG1 mRNA and promotes oxaliplatin resistance in hepatocellular carcinoma. This PRMT3-IGF2BP1-HEG1 axis was identified as a key driver of oxaliplatin resistance. CRISPR/Cas9 activation library screening; site-directed mutagenesis (R452 methylation site); in vitro and in vivo functional validation; mRNA stability assays Nature communications Medium 37024475
2023 PRMT3 methylates RIG-I at R730, MDA5 at R822, and cGAS at R111 via asymmetric dimethylation. These modifications reduce RNA-binding ability of RIG-I and MDA5 and reduce DNA-binding ability and oligomerization of cGAS, leading to inhibition of downstream type I interferon production. Mice with loss of one copy of Prmt3 or treated with SGC707 show increased resistance to RNA and DNA virus infection. Co-immunoprecipitation; in vitro methylation assays; RNA/DNA binding assays; mutagenesis of methylation sites; in vivo mouse viral challenge models Proceedings of the National Academy of Sciences of the United States of America High 37639603
2023 PRMT3 interacts with METTL14 and mediates its arginine methylation. PRMT3 inhibition leads to METTL14 overexpression, which promotes m6A methylation via an m6A-YTHDF2-dependent mechanism, reducing GPX4 mRNA stability and increasing lipid peroxidation/ferroptosis in endometrial cancer cells. Co-immunoprecipitation; PRMT3 inhibition (SGC707); m6A-seq/YTHDF2 mechanistic studies; mRNA stability assays; xenograft mouse models Advanced science Medium 37973560
2024 PRMT3 methylates HSP60 at R446, inducing HSP60 oligomerization and maintaining mitochondrial homeostasis. Targeting PRMT3-dependent HSP60 methylation disrupts mitochondrial integrity, increases mitochondrial DNA leakage, and activates cGAS/STING-mediated anti-tumor immunity. Co-immunoprecipitation; site-directed mutagenesis (R446); mitochondrial integrity assays; mtDNA leakage measurement; cGAS/STING pathway analysis; mouse tumor models Nature communications Medium 39256398
2024 PRMT3 directly methylates PDHK1 (pyruvate dehydrogenase kinase 1) at R363 and R368 via asymmetric dimethylation, increasing PDHK1 kinase activity and lactate production. Elevated lactate promotes H3K18 lactylation at the PD-L1 promoter, enhancing PD-L1 expression and tumor immune evasion in hepatocellular carcinoma. Co-immunoprecipitation; site-directed mutagenesis (R363/368K); PDHK1 kinase activity assays; RNA-seq; ChIP assay for H3K18la at PD-L1 promoter; PRMT3 KO mouse model Cell death & disease Medium 40050608
2024 ZNF200, an uncharacterized nuclear protein, interacts with PRMT3 via the N-terminal zinc finger domain of PRMT3 binding to the C-terminal zinc finger regions of ZNF200. ZNF200 stabilizes PRMT3 by inhibiting its proteasomal degradation and promotes nuclear translocation of PRMT3, leading to increased global H4R3me2a modifications. Yeast two-hybrid; co-immunoprecipitation; GST pull-down; molecular docking; proteasomal degradation assays; H4R3me2a ChIP/western The Biochemical journal Medium 39513743
2021 PRMT3 promotes colorectal cancer tumorigenesis by stabilizing c-MYC protein. The pro-tumorigenic function of PRMT3 is dependent on c-MYC. PRMT3 overexpression/knockdown; c-MYC protein stability assays; epistasis by c-MYC rescue experiments Gene Low 33991650
2021 PRMT3 promotes colorectal cancer progression by methylating HIF1α at R282, which is necessary for HIF1α stabilization and its oncogenic function. PRMT3-mediated tumorigenesis in colorectal cancer is dependent on HIF1α methylation. In vitro methylation assays; site-directed mutagenesis (R282); HIF1α stability assays; tumor models Cell death & disease Medium 34753906
2022 PRMT3 promotes glioblastoma progression by reprogramming metabolic pathways to increase glycolysis via upregulating HIF1α expression. PRMT3 knockdown reduces proliferation, migration, and tumor growth in xenograft models. PRMT3 knockdown/overexpression; metabolic flux analysis; HIF1α pathway analysis; xenograft mouse models; SGC707 pharmacological inhibition Cell death & disease Low 36351894
2025 PRMT3 promotes HIV-1 latency reversal by interacting with the HIV-1 promoter and increasing H4R3me2a levels and P-TEFb recruitment at the viral promoter. PRMT3 forms a transcriptional hub with TEAD4 and P-TEFb at the HIV-1 promoter, with TEAD4 recognition motifs mediating PRMT3 and TEAD4 co-recruitment. Physical interactions among PRMT3, P-TEFb, and TEAD4 were confirmed. dCas9-targeted locus-specific protein analysis; co-immunoprecipitation (PRMT3-P-TEFb, PRMT3-TEAD4); ChIP for H4R3me2a and P-TEFb; ATAC-seq for chromatin accessibility; primary cell latency reversal assays Nature communications Medium 40374607
2025 PRMT3 mediates arginine methylation of TFAP2A transcription factor, enhancing its binding to the IDO1 promoter, prolonging TFAP2A half-life, increasing its nuclear localization and dimer formation, ultimately upregulating IDO1 expression and kynurenine synthesis to promote radioresistance and immune suppression in non-small cell lung cancer. Co-immunoprecipitation; in vitro methylation of TFAP2A; protein stability/half-life assays; ChIP at IDO1 promoter; kynurenine measurement; in vivo tumor models Cancer research Medium 41129671
2025 PRMT3 mediates arginine methylation of FOXO1 at R253, promoting FOXO1 degradation and inhibiting its nuclear translocation, thereby impairing decidualization of endometrial stromal cells through oxidative stress. SGC707 inhibits endometriosis in animal models. Co-immunoprecipitation; site-directed mutagenesis (R253); FOXO1 stability and nuclear localization assays; decidualization assays; in vivo endometriosis mouse model with SGC707 Cellular and molecular life sciences : CMLS Medium 41455763
2025 PRMT3 drives H4R3me2a-mediated upregulation of miR-448, which suppresses IGF1R, leading to GSK3β activation and tau hyperphosphorylation via PI3K/AKT/GSK3β signaling in primary age-related tauopathy. SGC707 reduces tau hyperphosphorylation in vivo. Transcriptomic profiling; ChIP for H4R3me2a; miR-448 functional studies; IGF1R suppression; GSK3β/tau phosphorylation assays; in vivo SGC707 treatment Advanced science Medium 40344412
2026 PRMT3 catalyzes asymmetric dimethylation of PCSK9 at R582, which prevents binding of E3 ligase CHIP to PCSK9 at K575, thereby blocking ubiquitination-mediated degradation of PCSK9 and stabilizing this procalcific factor to promote aortic valve calcification. Immunoprecipitation-MS to identify PCSK9 as substrate; co-immunoprecipitation; site-directed mutagenesis (R582K, K575A); PCSK9 half-life assays; enzymatically inactive PRMT3 variant; Prmt3 haploinsufficiency mouse model; SGC707 and PROTAC treatment Circulation High 41797709
2026 Feeding upregulates PRMT3 via insulin-pAKT signaling, while fasting reduces PRMT3 and ADMA-containing proteins. PRMT3 drives expression of citrate transporter SLC25A1 through direct arginine methylation during feeding. Pharmacological PRMT3 inhibition attenuates diet-induced obesity and enhances adipocyte glycolysis. Adipocyte-specific Slc25a1 deletion protects against diet-induced obesity and enhances insulin sensitivity. In vivo mouse models (diet-induced obesity, time-restricted feeding); PRMT3 inhibition with SGC707; adipocyte-specific Slc25a1 KO; ADMA proteomics; insulin-pAKT signaling pathway analysis Nature communications Medium 41629293

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Crystal structure of the conserved core of protein arginine methyltransferase PRMT3. The EMBO journal 263 10899106
2004 PRMT3 is a ribosomal protein methyltransferase that affects the cellular levels of ribosomal subunits. The EMBO journal 145 15175657
2005 Ribosomal protein S2 is a substrate for mammalian PRMT3 (protein arginine methyltransferase 3). The Biochemical journal 140 15473865
1999 Unusual sites of arginine methylation in Poly(A)-binding protein II and in vitro methylation by protein arginine methyltransferases PRMT1 and PRMT3. The Journal of biological chemistry 140 10224081
2007 Ribosomal protein rpS2 is hypomethylated in PRMT3-deficient mice. The Journal of biological chemistry 113 17439947
2000 PRMT3 is a distinct member of the protein arginine N-methyltransferase family. Conferral of substrate specificity by a zinc-finger domain. The Journal of biological chemistry 111 10931850
2015 A potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3). Angewandte Chemie (International ed. in English) 101 25728001
2004 DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo. Oncogene 96 15334060
2023 PRMT3-mediated arginine methylation of IGF2BP1 promotes oxaliplatin resistance in liver cancer. Nature communications 76 37024475
2023 PRMT3-Mediated Arginine Methylation of METTL14 Promotes Malignant Progression and Treatment Resistance in Endometrial Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 61 37973560
2022 PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism. Cell death & disease 56 36351894
2019 Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648. Cell death & disease 55 31378783
2013 Exploiting an allosteric binding site of PRMT3 yields potent and selective inhibitors. Journal of medicinal chemistry 52 23445220
2014 PRMT3 regulates hepatic lipogenesis through direct interaction with LXRα. Diabetes 41 25187371
2008 PRMT3 inhibits ubiquitination of ribosomal protein S2 and together forms an active enzyme complex. Biochimica et biophysica acta 38 18573314
2024 Targeting PRMT3 impairs methylation and oligomerization of HSP60 to boost anti-tumor immunity by activating cGAS/STING signaling. Nature communications 35 39256398
2009 Type I Arginine Methyltransferases PRMT1 and PRMT-3 Act Distributively. The Journal of biological chemistry 35 19158082
2021 PRMT3 promotes tumorigenesis by methylating and stabilizing HIF1α in colorectal cancer. Cell death & disease 31 34753906
2018 Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3). Journal of medicinal chemistry 31 29244490
2010 PRMT3 is essential for dendritic spine maturation in rat hippocampal neurons. Brain research 30 20647003
2020 Zebrafish prmt3 negatively regulates antiviral responses. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 32643209
2018 The 40S ribosomal protein uS5 (RPS2) assembles into an extraribosomal complex with human ZNF277 that competes with the PRMT3-uS5 interaction. The Journal of biological chemistry 28 30530495
2021 Arginine methyltransferase PRMT3 promote tumorigenesis through regulating c-MYC stabilization in colorectal cancer. Gene 25 33991650
2025 PRMT3 drives PD-L1-mediated immune escape through activating PDHK1-regulated glycolysis in hepatocellular carcinoma. Cell death & disease 24 40050608
2021 PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling. Communications biology 22 33495566
2024 PRMT3 methylates HIF-1α to enhance the vascular calcification induced by chronic kidney disease. Molecular medicine (Cambridge, Mass.) 17 38200452
2023 Asymmetric arginine dimethylation of cytosolic RNA and DNA sensors by PRMT3 attenuates antiviral innate immunity. Proceedings of the National Academy of Sciences of the United States of America 16 37639603
2023 PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast. Cancer science 14 36637351
2011 The C. elegans PRMT-3 possesses a type III protein arginine methyltransferase activity. Journal of receptor and signal transduction research 13 21385054
2019 Inhibition of PRMT3 activity reduces hepatic steatosis without altering atherosclerosis susceptibility in apoE knockout mice. Biochimica et biophysica acta. Molecular basis of disease 12 30776415
2022 PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice. Scientific reports 11 35013582
2023 Arginine methyltransferases PRMT2 and PRMT3 are essential for biosynthesis of plant-polysaccharide-degrading enzymes in Penicillium oxalicum. PLoS genetics 7 37523410
2024 Discovery of PRMT3 Degrader for the Treatment of Acute Leukemia. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 6 39120042
2014 PRMT3: new binding molecule to RhoGDI-α during mycophenolic acid-induced β-cell death. Transplantation proceedings 6 24815167
2019 Cisplatin-induced ototoxicity involves interaction of PRMT3 and cannabinoid system. Archives of toxicology 5 31256211
2010 Tyrosine 87 is vital for the activity of human protein arginine methyltransferase 3 (PRMT3). Biochimica et biophysica acta 5 21059412
2025 PRMT3 and CARM1: Emerging Epigenetic Targets in Cancer. Journal of cellular and molecular medicine 4 39964832
2025 PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub. Nature communications 3 40374607
2026 PRMT3 Drives IDO1-Dependent Radioresistance and Immunosuppression by Promoting Kynurenine Metabolism in Non-Small Cell Lung Cancer. Cancer research 1 41129671
2026 PRMT3 at the crossroads of inflammation: dual roles in metabolic reprogramming and immune dysregulation in chronic diseases. Frontiers in immunology 1 41583428
2025 PRMT3-Mediated H4R3me2a Promotes Primary Age-Related Tauopathy by Driving Tau Hyperphosphorylation in Neuron. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40344412
2025 CircERBB3 Targets miR-194-5p/PRMT3 to Promote Hepatocellular Carcinoma Progression. Journal of physiological investigation 1 40616280
2025 PRMT3-mediated FOXO1 arginine methylation exacerbates oxidative stress-induced decidualization defects in the eutopic endometrium of endometriosis. Cellular and molecular life sciences : CMLS 1 41455763
2024 Chicken PRMT3 facilitates IBDV replication. Poultry science 1 38981362
2021 Identification of a cartilage specific novel miRNA which directly targets PRMT3 in rats. Osteoarthritis and cartilage open 1 36474992
2026 PRMT3-mediated post-translational adaptation to fasting regulates metabolic flexibility. Nature communications 0 41629293
2026 PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification. Circulation 0 41797709
2025 Interplay of PRMTs and Identification of Biomarkers Through Machine Learning Algorithms in Pan-Cancer, Highlighting PRMT3 as a Biomarker in Pancreatic Cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41099588
2024 The uncharacterized protein ZNF200 interacts with PRMT3 and aids its stability and nuclear translocation. The Biochemical journal 0 39513743