Affinage

WDR77

Methylosome protein WDR77 · UniProt Q9BQA1

Length
342 aa
Mass
36.7 kDa
Annotated
2026-06-11
53 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WDR77 (MEP50/p44) is an obligate WD40 β-propeller cofactor of the protein arginine methyltransferase PRMT5, assembling into a ~450 kDa hetero-octameric complex of four PRMT5 and four MEP50 subunits in which MEP50's seven-bladed β-propeller contacts the PRMT5 N-terminal domain and positions protein substrates toward the catalytic site (PMID:23071334, PMID:29518110). PRMT5 has negligible methyltransferase activity alone, and MEP50 acts as an obligate activator: a conserved Arg-42 on the MEP50 insertion loop lowers the substrate Km, and the W54 residue buried in the PRMT5 TIM-barrel pocket defines the activating interface (PMID:25713080, PMID:28271477). Through this complex WDR77 directs symmetric arginine dimethylation of histones (H2A, H4R3me2s, H3R2me1) and a broad set of non-histone substrates including nucleoplasmin, ZNF326, GLI1, the HEV ORF1 replicase, and Lsm11/SmE, thereby shaping chromatin marks, alternative splicing, Hedgehog signaling, and antiviral restriction (PMID:22009756, PMID:27270440, PMID:28977470, PMID:30675521, PMID:37276230, PMID:37562960). The H4R3me2s mark deposited by PRMT5-WDR77 is read by the PHF1 PHD finger in concert with the CRL4B complex to repress target genes, and its loss de-represses transcription (PMID:29846670). WDR77 activity is tuned post-translationally: SIRT7 deacetylates WDR77 at K3/K243 to weaken PRMT5 binding, RNF187 ubiquitinates WDR77 at K118 (K48-linked) for proteasomal degradation, and the scaffold TBL2 and adaptor C6orf223 enhance PRMT5-WDR77 assembly and activity (PMID:30282801, PMID:40197797, PMID:39499734, PMID:41090362). Independent of methyltransferase function, WDR77 binds the proline-rich region of MAVS via its WD2-WD3-WD4 module to suppress prion-like MAVS aggregation and dampen RIG-I-MAVS antiviral signaling, and partners with PRMT5 and Argonaute2 as an RNA-binding complex that drives PDCD1 (PD-1) mRNA decay in T cells (PMID:37563140, PMID:41623183). Subcellular localization governed by NLS/NES sequences partitions WDR77 function—cytoplasmic WDR77 drives proliferation while nuclear WDR77 supports differentiation and acts as an androgen receptor coactivator (PMID:21789256, PMID:23734213, PMID:40934084). A germline WDR77 R198H missense mutation impairs PRMT5 binding and reduces cellular H4R3me2, linking WDR77 dysfunction to human disease (PMID:34326253).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 Medium

    Before its structural role was known, MEP50 was placed within PRMT5-dependent transcriptional repression, establishing it as a histone-binding partner of the methyltransferase.

    Evidence Co-IP and in vitro histone-binding assays showing SUZ12 and selective H2A binding

    PMID:16712789

    Open questions at the time
    • No structural basis for histone selectivity
    • Mechanism of repression not resolved at this stage
  2. 2011 Medium

    The first reconstituted activity defined PRMT5-MEP50 substrate scope, showing the complex methylates pre-deposition histones and the chaperone nucleoplasmin, and that localization signals partition WDR77 function between proliferation and differentiation.

    Evidence Xenopus complex isolation with MS site mapping and in vitro methylation; NLS/NES mutagenesis with AR reporter assays

    PMID:21789256 PMID:22009756

    Open questions at the time
    • Did not establish atomic architecture of the complex
    • Determinants of nuclear vs cytoplasmic partitioning incompletely mapped
  3. 2012 High

    Crystallography solved the hetero-octameric architecture and revealed how MEP50's β-propeller engages the PRMT5 N-terminal domain to recognize substrate, answering how the cofactor enables catalysis.

    Evidence X-ray structure of human PRMT5:MEP50 with SAM analog and H4 peptide

    PMID:23071334

    Open questions at the time
    • Did not quantify the kinetic contribution of MEP50 residues
    • Non-histone substrate positioning not addressed
  4. 2012 Medium

    In vivo knockout work established WDR77 as a regulator of proliferation versus differentiation, placing it upstream of the p21/Rb and NF-κB axes in prostate and astrocyte contexts.

    Evidence Conditional and germline KO mouse models, shRNA epistasis, subcellular fractionation, cell cycle analysis

    PMID:20519372 PMID:22665061 PMID:22751923 PMID:23145110

    Open questions at the time
    • Molecular link between localization and p21/NF-κB output unresolved
    • Whether phenotypes depend on PRMT5 catalysis not dissected
  5. 2015 High

    Reconstitution with mutagenesis proved MEP50 is an obligate activator that positions substrate, pinpointing Arg-42 as a determinant of the substrate Km and showing PRMT5 alone is inactive.

    Evidence Kinetic in vitro methylation, MEP50 Arg-42 mutagenesis, histone peptide arrays

    PMID:25713080

    Open questions at the time
    • Nucleosomes are not substrates—physiological substrate presentation unresolved
    • Did not address non-histone substrate kinetics
  6. 2016 Medium

    Chromatin-level studies connected PRMT5-MEP50 catalysis to opposing transcriptional outcomes, with H3R2me1 recruiting WDR5 for activation and H4R3me2s mediating repression downstream of TGFβ.

    Evidence ChIP-seq, RNA-seq, PRMT5/MEP50 knockdown; separate knockdown TGFβ-sensitivity assays

    PMID:24944016 PMID:27270440

    Open questions at the time
    • Locus-specific determinants of activation vs repression unclear
    • Recruitment of the complex to specific genes not defined
  7. 2017 High

    Substrate scope was extended beyond histones, with ZNF326 methylation at R175 linking WDR77 to alternative splicing fidelity.

    Evidence MS substrate identification, Co-IP, methylation and RNA-seq splicing analysis with knockdown

    PMID:28977470

    Open questions at the time
    • How methylation alters ZNF326 function mechanistically not resolved
    • Breadth of splicing targets not exhaustively mapped
  8. 2018 Medium

    Regulation of WDR77 activity was established at two layers: SIRT7 deacetylation weakening PRMT5 binding, and PHF1/CRL4B reading the H4R3me2s mark to repress target genes.

    Evidence In vitro deacetylation, K3R/K243R mutagenesis and KO rescue; histone peptide binding and ChIP-seq for reader/effector complex

    PMID:29846670 PMID:30282801

    Open questions at the time
    • Signals controlling SIRT7-WDR77 deacetylation unknown
    • Stoichiometry of PHF1-PRMT5-CRL4B unit not determined
  9. 2019 Medium

    Non-histone signaling control was demonstrated, with PRMT5-MEP50 methylation of GLI1 blocking its ubiquitin-ligase binding to drive Hedgehog pathway activation.

    Evidence Co-IP, methylation, fractionation, and ubiquitination assays

    PMID:30675521

    Open questions at the time
    • GLI1 methylation site not pinpointed in this summary
    • Single-lab functional link awaits independent validation
  10. 2021 Medium

    WDR77 abundance was shown to be controlled by degradation pathways co-opted in disease, with HBx routing WDR77 to a DDB1 E3 ligase to relieve H4R3me2s repression on HBV cccDNA; a germline R198H mutation independently impairs PRMT5 binding in patients.

    Evidence Co-IP, ChIP, and HBV replication models; whole-exome sequencing, Co-IP and patient-tissue H4R3me2 Western

    PMID:34326253 PMID:34373747

    Open questions at the time
    • Disease phenotype of R198H carriers not fully characterized
    • Generality of DDB1-mediated degradation beyond HBV unclear
  11. 2022 Medium

    The PRMT5:MEP50 interface was validated as druggable, and WDR77 was placed at active promoter regions co-occupying genes with MafB and β-catenin.

    Evidence Virtual screening and docking with W54-targeting inhibitor (Compound 17); reciprocal Co-IP and ChIP-seq of MafB/β-catenin/WDR77

    PMID:35482762 PMID:36206451

    Open questions at the time
    • Functional consequence of MafB/β-catenin/WDR77 co-occupancy not mechanistically resolved
    • Selectivity window of interface inhibitors in vivo unclear
  12. 2023 High

    A methyltransferase-independent innate-immune role emerged, with WDR77 binding the MAVS proline-rich region through its WD2-WD4 module to suppress prion-like MAVS aggregation; the complex was also shown to restrict HEV and modify Lsm11/SmE.

    Evidence In vitro filament assays with recombinant proteins, domain mapping, myeloid KO mice; HEV replicon and R458K rescue; cryo-EM of Lsm10/Lsm11-methylosome

    PMID:37276230 PMID:37562960 PMID:37563140

    Open questions at the time
    • How WDR77 toggles between methyltransferase and MAVS-suppressive roles unknown
    • Regulation of WDR77 recruitment to MAVS upon infection incomplete
  13. 2024 Medium

    Assembly of the active complex was shown to be promoted by accessory scaffolds, with TBL2 enhancing PRMT5-WDR77 interaction and downstream AKT phosphorylation.

    Evidence Proteomics, Co-IP, methyltransferase assay, in vivo and in vitro proliferation assays

    PMID:39499734

    Open questions at the time
    • Whether TBL2 directly bridges the two subunits structurally unresolved
    • Link from methylation to AKT phosphorylation indirect
  14. 2025 Medium

    Multiple new regulatory and functional dimensions converged: RNF187 K118 ubiquitination degrades WDR77 to relieve EGR1 repression, C6orf223 stabilizes the complex, WDR77 acts with PRMT5/Ago2 to drive PDCD1 mRNA decay, and WDR77 directly coactivates AR cistromes in prostate cancer.

    Evidence Co-IP/MS ubiquitination mapping with EGR1 reporter; domain-mapped Co-IP and activity assay; RIP, RNA decay, T-cell conditional KO; ChIP-seq AR/WDR77 cistromes in organoids and PDX

    PMID:40197797 PMID:40934084 PMID:41090362 PMID:41623183

    Open questions at the time
    • Interplay between competing stabilizers (TBL2, C6orf223) and degraders (RNF187) not integrated
    • How RNA-binding versus methyltransferase functions are partitioned in vivo unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how WDR77 localization, post-translational modification, and accessory-protein binding are coordinated to switch the complex between its methyltransferase, RNA-decay, transcriptional coactivator, and MAVS-suppressive activities in a given cell context.
  • No unifying model linking localization signals to functional switching
  • Quantitative competition between activating and degrading partners undefined
  • In vivo substrate hierarchy of the complex not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 5 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 3 GO:0003723 RNA binding 1 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 3 GO:0005829 cytosol 3
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 3
Partners
ARC6ORF223MAVSPHF1PRMT5RNF187SIRT7TBL2
Complex memberships
PRMT5-MEP50 (WDR77) methylosomePRMT5/MEP50/pICln methylosome

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Crystal structure of the human PRMT5:MEP50 hetero-octameric complex (4 PRMT5 + 4 MEP50) bound to an SAM analog and histone H4 peptide substrate revealed that MEP50's seven-bladed β-propeller interacts with the N-terminal domain of PRMT5, delineating structural elements of substrate recognition. X-ray crystallography with bound cofactor analog and peptide substrate Proceedings of the National Academy of Sciences of the United States of America High 23071334
2018 Cryo-EM structure of the human PRMT5:MEP50 complex at 3.7 Å confirmed the 450 kDa hetero-octameric assembly with D2 internal symmetry; MEP50 subunits are arranged peripherally in complex with the PRMT5 N-terminal domain, consistent with the crystal structure. Single-particle cryo-electron microscopy PloS one High 29518110
2015 MEP50 is required for efficient histone methylation by PRMT5; the cross-dimer MEP50 is paired with its cognate PRMT5 to promote histone methylation. Mutation of a conserved arginine (Arg-42) on the MEP50 insertion loop increased the histone substrate Km, impairing PRMT5-MEP50 enzymatic efficiency. Neither full-length human PRMT5 nor the Xenopus PRMT5 catalytic domain has appreciable protein methyltransferase activity alone. Histones H4 and H3 bind PRMT5-MEP50 via histone fold interactions, and nucleosomes are not substrates. In vitro methylation assays including continuous kinetic assay, site-directed mutagenesis of MEP50 Arg-42, competition experiments, high-density histone peptide array interaction studies The Journal of biological chemistry High 25713080
2011 Xenopus Prmt5-Mep50 complex isolated from eggs specifically methylates pre-deposition histones H2A/H2A.X-F and H4, and the histone chaperone nucleoplasmin at Arg-187 (mono- and symmetric dimethylation). Nucleoplasmin modulates Prmt5-Mep50 activity directed toward histones, consistent with a regulatory role. Biochemical complex isolation, mass spectrometry identification of methylation sites, in vitro methylation assays The Journal of biological chemistry High 22009756
2016 PRMT5-MEP50 catalyzes histone mono- and dimethylation (H3R2me1 and H4R3me2s) at chromatin of metastasis suppressor and EMT genes in response to TGFβ; H3R2me1 recruits WDR5 for concomitant H3K4 methylation and transcriptional activation, while H4R3me2s suppresses transcription at distinct loci. ChIP-seq, RNA-seq, knockdown of PRMT5 and MEP50, chromatin immunoprecipitation for histone marks Oncogene High 27270440
2017 Nuclear PRMT5/WDR77 complex symmetrically dimethylates ZNF326 at Arg-175 (R175me2s), a modification lost upon PRMT5 or WDR77 depletion; loss of either subunit causes defects in alternative splicing including inclusion of A-T rich exons in target genes, phenocopying ZNF326 loss. Mass spectrometry identification of ZNF326 as substrate, Co-IP, methylation assays, RNA-seq splicing analysis, knockdown Nucleic acids research High 28977470
2018 SIRT7 directly deacetylates WDR77 at Lys-3 and Lys-243; this deacetylation reduces WDR77's interaction with PRMT5, suppresses WDR77/PRMT5 transmethylase activity and H4R3me2 levels, and reduces colon cancer cell proliferation and migration. WDR77-2KR (K3R/K243R) variant showed reduced PRMT5 interaction and activity compared to WT. Co-immunoprecipitation, in vitro deacetylation assay, site-directed mutagenesis (K3R, K243R), H4R3me2 methylation assay, KO rescue experiments The Journal of biological chemistry High 30282801
2019 MEP50/PRMT5 complex associates with GLI1 and methylates it; methylated GLI1 loses its ability to bind ubiquitin ligase ITCH/NUMB, resulting in nuclear accumulation and activation of GLI1 in the Hedgehog signaling pathway. HH signals enhance MEP50/PRMT5-GLI1 association. Co-immunoprecipitation, methylation assays, nuclear/cytoplasmic fractionation, ubiquitination assays Communications biology Medium 30675521
2018 PHF1 N-terminal PHD finger recognizes H4R3me2s catalyzed by PRMT5-WDR77; PHF1, PRMT5-WDR77, and CRL4B complex (DDB1/CUL4B) reciprocally interact and collaborate as a functional unit to regulate target genes including E-cadherin and FBXW7. Co-IP, histone peptide binding assays, ChIP-seq, genome-wide target analysis, knockdown/overexpression Nucleic acids research Medium 29846670
2021 HBx drives the cellular DDB1-containing E3 ubiquitin ligase to degrade WDR77 by recruiting WDR77 to the DDB1 complex; WDR77 degradation disables PRMT5-triggered H4R3me2s on cccDNA minichromosome, releasing transcriptional repression and promoting HBV replication. Co-IP, Western blot, ChIP assay, Southern/Northern blot, immunofluorescence in PHHs, HepG2-NTCP cells, and human liver-chimeric mice Theranostics Medium 34373747
2023 WDR77 binds to the proline-rich region of MAVS through its WD2-WD3-WD4 domain and inhibits the formation of prion-like MAVS filaments in vitro; upon virus infection, WDR77 is recruited to MAVS to prevent prion-like aggregation and downregulate RIG-I-MAVS signaling. Myeloid-specific Wdr77-deficient mice showed enhanced antiviral responses to negative-strand RNA viruses. Co-IP (MAVS-WDR77 interaction), in vitro filament formation assay with recombinant proteins, domain mapping, myeloid-specific KO mouse model Nature communications High 37563140
2023 PRMT5/WDR77 complex catalyzes methylation of HEV ORF1 replicase at Arg-458 (R458), impairing its replicase activity; virus bearing R458K mutation in ORF1 relieves PRMT5/WDR77-dependent restriction of HEV replication. SILAC/mass spectrometry identification, HEV replicon system, ORF1 methylation assay, R458K mutant virus rescue experiment PLoS pathogens Medium 37276230
2023 The PRMT5/MEP50/pICln methylosome methylates two arginine residues in the N-terminal region of Lsm11 and an N-terminal arginine in SmE (a modification distinct from spliceosomal snRNP biogenesis); the Lsm10-Lsm11 heterodimer interaction with the methylosome is mediated by PRMT5. Biochemical interaction assays, cryo-EM structural analysis of Lsm10/Lsm11-methylosome complex, in vitro methylation assays RNA (New York, N.Y.) High 37562960
2021 WDR77 germ-line missense mutation R198H impairs its interaction with PRMT5, and a splice-site mutation causes exon 6 skipping leading to markedly decreased mutant mRNA and obviously reduced H4R3me2 levels in mutation carriers. Whole-exome sequencing, Co-IP of R198H mutant vs WT for PRMT5 interaction, H4R3me2 Western blot in patient-derived tissue Proceedings of the National Academy of Sciences of the United States of America Medium 34326253
2011 p44/WDR77 contains functional nuclear localization signals (NLS) and nuclear exclusion signals (NES); site-directed mutagenesis of critical NLS residues abolished nuclear localization and transcriptional coactivator activity for AR. p44/WDR77 localizes cytoplasmically during prostate proliferation and translocates to the nucleus during differentiation. Subcellular localization assays spanning full ORF, NLS/NES mutagenesis, AR transcriptional reporter assays, MALDI-TOF/TOF mass spectrometry of NLS/NES-associated proteins PloS one Medium 21789256
2012 Cytoplasmic p44/WDR77 is essential for proliferation of prostate epithelial cells, while nuclear p44/WDR77 is required for cell differentiation and prostate-specific protein secretion; loss of p44/WDR77 leads to cell growth arrest partially through the p21-Rb signaling pathway. Conditional KO mouse model, re-expression rescue experiments, subcellular fractionation, cell cycle analysis PloS one Medium 22665061 23145110
2012 Deletion of p44/WDR77 gene causes premature death with dramatic astrogliosis; loss of p44/WDR77 in astrocytes leads to growth arrest and astrocyte activation associated with upregulation of p21(Cip1) expression and NF-κB activation. Silencing p21(Cip1) or NF-κB p65 with shRNA abolished astrocyte activation and rescued growth inhibition. Gene knockout mouse model, shRNA knockdown epistasis experiment, Western blot, GFAP immunostaining Molecular and cellular biology Medium 22751923
2010 p44/WDR77-null mouse prostates showed smaller glands with fewer branches, less differentiation, hyperproliferation, and altered expression of androgen-regulated genes, indicating that WDR77 plays a role in prostate growth and differentiation by modulating AR-target gene expression. Conditional KO mouse model, histology, gene expression analysis Endocrinology Medium 20519372
2006 SUZ12 interacts with MEP50 both in vitro and in vivo; MEP50 binds histone H2A selectively among core histones and mediates transcriptional repression by PRMT5. Co-immunoprecipitation (in vivo), in vitro binding assays, histone binding specificity assay Biochemical and biophysical research communications Medium 16712789
2003 MEP50 was identified as a novel FCP1-interacting protein by mass spectrometry of affinity-purified FCP1 complexes; FCP1 specifically interacts with components of spliceosomal U snRNPs, suggesting a role in linking transcription elongation with splicing. Affinity purification of epitope-tagged FCP1, mass spectrometry identification Nucleic acids research Low 12560496
2017 The structure of the PRMT5:MEP50 hetero-octameric complex provides a basis for understanding how MEP50's β-propeller positions substrate arginines toward the PRMT5 catalytic site; MEP50 W54 burial into a hydrophobic pocket of the PRMT5 TIM barrel defines a protein-protein interaction interface targetable by small molecules. Structural analysis review; small-molecule virtual screen + molecular docking validating the PPI interface Sub-cellular biochemistry Medium 28271477
2022 Compound 17, a small-molecule PRMT5:MEP50 PPI inhibitor, disrupts MEP50 W54 burial into the PRMT5 TIM barrel hydrophobic pocket, selectively inhibiting PRMT5:MEP50 substrate methylation (IC50 <500 nM in cancer cells) and confirming the MEP50-PRMT5 interface as a druggable site. Virtual screening, molecular docking, in vitro methylation inhibition assays, RNA-seq Journal of medicinal chemistry Medium 36206451
2021 The interface between the TIM barrel of PRMT5 and adaptor proteins pICln, RioK1, and COPR5 involves the consensus amino acid sequence GQF[D/E]DA[E/D]; protein crystallography of the RioK1-derived peptide revealed a novel PPI site on PRMT5. Peptide truncation and mutation studies, protein crystallography Chembiochem : a European journal of chemical biology High 33624332
2024 TBL2 acts as a scaffolding protein that promotes PRMT5 and WDR77 interaction; this enhances PRMT5 methyltransferase activity, leading to increased AKT phosphorylation in breast cancer cells. Proteomic analysis, co-immunoprecipitation, methyltransferase activity assay, in vivo and in vitro proliferation assays Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39499734
2016 WDR77 was identified as a protein interacting with TSC22D2 by yeast two-hybrid screening; the interaction was confirmed by co-immunoprecipitation and co-localization by immunofluorescence. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence Tumour biology Low 27337956
2013 The N-terminal region of p44/WDR77 (not the C-terminal WD40 domain) mediates interaction with the N-terminus of AR and full-length Smad1, forming a ternary AR-p44-Smad1 complex; both N- and C-terminal domains are needed for maximum AR transcriptional activation, while the central portion is required for nuclear p44-mediated prostate cancer growth inhibition. Yeast two-hybrid, co-immunoprecipitation, luciferase reporter assays, deletion mutagenesis, cell proliferation assays PloS one Medium 23734213
2014 Silencing p44/WDR77 increased cellular sensitivity to TGFβ signaling, inducing Smad2/3 phosphorylation, TGFβ-mediated transcription, and TGFβ2 and TβRII expression, suggesting WDR77 downregulates TGFβ ligand and receptor expression to restrict TGFβ pathway activity in proliferating cells. shRNA knockdown, phospho-Smad Western blot, TGFβ-responsive reporter assay, qPCR Biochemical and biophysical research communications Medium 24944016
2025 RNF187 interacts with WDR77 and catalyzes lysine 48-linked polyubiquitination of WDR77 at K118, mediating its proteasomal degradation. Decreased WDR77 reduces H4R3me2s by PRMT5, relieving transcriptional repression of EGR1 and thereby promoting human spermatogonial stem cell proliferation and migration. Co-immunoprecipitation, mass spectrometry, ubiquitination site mapping (K118), proteasome inhibitor experiments, H4R3me2s Western blot, EGR1 reporter Cell proliferation Medium 40197797
2025 WDR77 directly interacts with AR and when this interaction is disrupted, AR-WDR77 complex formation is prevented, reducing AR DNA-binding, AR-dependent gene expression, and cell proliferation; AR and WDR77 cistromes overlap considerably at AR-regulated genes associated with aggressive prostate cancer. Co-immunoprecipitation, ChIP-seq (AR and WDR77 cistromes), disruption of WDR77-AR interaction, organoid models, patient-derived xenograft growth assays Cell reports Medium 40934084
2022 MafB, β-catenin, and WDR77 interact directly with each other and share similar genomic binding profiles; their common target sites are enriched just downstream of transcription initiation sites near paused RNA polymerase and the +1 nucleosome, and occupancy correlates with transcriptional activity. Co-immunoprecipitation, ChIP-seq for all three factors PloS one Medium 35482762
2025 PRMT5 is prone to aggregation when expressed at supra-stoichiometric levels relative to its obligate partner MEP50/WDR77; co-increased expression of PRMT5 and MEP50 mitigates protein aggregation induced by chromosomal instability, rendering cancer cells less sensitive to proteasome inhibitors. Protein aggregation assays, co-expression studies, proteasome inhibitor sensitivity assays in CIN models bioRxivpreprint Low bio_10.1101_2025.09.12.675799
2025 PRMT5 acts as an RNA-binding protein in a methyltransferase activity-independent manner and promotes PDCD1 (PD-1) mRNA decay together with WDR77 and Argonaute2; the PRMT5/WDR77 complex binds a conserved AU-rich element in the PDCD1 3' UTR. IFN/STAT1 signaling transcriptionally activates PRMT5 and WDR77, enhancing their binding to PDCD1 mRNA. Conditional KO of WDR77 in T cells disrupts T cell effector function and sensitizes tumors to anti-PD-1 therapy. RNA immunoprecipitation, RNA decay assay, conditional KO mouse model, 3' UTR reporter assay, Co-IP with Argonaute2 The Journal of clinical investigation Medium 41623183
2025 C6orf223 forms dimers through disulfide bonds; its N-terminal arginine-enriched region binds to the C-terminal negatively charged groove of PRMT5, stabilizing the PRMT5-MEP50 multiprotein complex and enhancing PRMT5 methyltransferase activity. Co-immunoprecipitation, domain-mapping, methyltransferase activity assay The Journal of clinical investigation Medium 41090362

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Crystal structure of the human PRMT5:MEP50 complex. Proceedings of the National Academy of Sciences of the United States of America 283 23071334
2016 A TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression. Oncogene 157 27270440
2017 Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging miR-124. Biochemical and biophysical research communications 132 29042195
2015 Histone H2A and H4 N-terminal tails are positioned by the MEP50 WD repeat protein for efficient methylation by the PRMT5 arginine methyltransferase. The Journal of biological chemistry 81 25713080
2017 The PRMT5/WDR77 complex regulates alternative splicing through ZNF326 in breast cancer. Nucleic acids research 72 28977470
2018 PHD finger protein 1 (PHF1) is a novel reader for histone H4R3 symmetric dimethylation and coordinates with PRMT5-WDR77/CRL4B complex to promote tumorigenesis. Nucleic acids research 71 29846670
2011 Protein arginine methyltransferase Prmt5-Mep50 methylates histones H2A and H4 and the histone chaperone nucleoplasmin in Xenopus laevis eggs. The Journal of biological chemistry 50 22009756
2011 Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer. PloS one 42 22022581
2016 Yeast two-hybrid screening identified WDR77 as a novel interacting partner of TSC22D2. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 36 27337956
2012 The p44/wdr77-dependent cellular proliferation process during lung development is reactivated in lung cancer. Oncogene 36 22665061
2021 HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver. Theranostics 32 34373747
2017 The Structure and Function of the PRMT5:MEP50 Complex. Sub-cellular biochemistry 32 28271477
2018 Sirtuin 7-mediated deacetylation of WD repeat domain 77 (WDR77) suppresses cancer cell growth by reducing WDR77/PRMT5 transmethylase complex activity. The Journal of biological chemistry 28 30282801
2018 Curcumin ameliorates PRMT5-MEP50 arginine methyltransferase expression by decreasing the Sp1 and NF-YA transcription factors in the A549 and MCF-7 cells. Molecular and cellular biochemistry 27 30392062
2006 Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that binds to histone H2A selectively in vitro. Biochemical and biophysical research communications 27 16712789
2010 Androgen receptor coactivator p44/Mep50 in breast cancer growth and invasion. Journal of cellular and molecular medicine 26 19840198
2019 MEP50/PRMT5-mediated methylation activates GLI1 in Hedgehog signalling through inhibition of ubiquitination by the ITCH/NUMB complex. Communications biology 24 30675521
2021 Biochemical Investigation of the Interaction of pICln, RioK1 and COPR5 with the PRMT5-MEP50 Complex. Chembiochem : a European journal of chemical biology 22 33624332
2010 Altered differentiation and proliferation of prostate epithelium in mice lacking the androgen receptor cofactor p44/WDR77. Endocrinology 22 20519372
2003 The FCP1 phosphatase interacts with RNA polymerase II and with MEP50 a component of the methylosome complex involved in the assembly of snRNP. Nucleic acids research 22 12560496
2022 Discovery and Biological Characterization of PRMT5:MEP50 Protein-Protein Interaction Inhibitors. Journal of medicinal chemistry 21 36206451
2011 Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77. PloS one 21 21789256
2017 Sulforaphane suppresses PRMT5/MEP50 function in epidermal squamous cell carcinoma leading to reduced tumor formation. Carcinogenesis 19 28854561
2021 Germ-line mutations in WDR77 predispose to familial papillary thyroid cancer. Proceedings of the National Academy of Sciences of the United States of America 17 34326253
2012 Subcellular localization of p44/WDR77 determines proliferation and differentiation of prostate epithelial cells. PloS one 16 23145110
2018 Cryo-electron microscopy structure of a human PRMT5:MEP50 complex. PloS one 15 29518110
2014 P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling. Biochemical and biophysical research communications 12 24944016
2024 HNRNPC promotes estrogen receptor-positive breast cancer cell cycle by stabilizing WDR77 mRNA in an m6A-dependent manner. Molecular carcinogenesis 11 38353359
2024 TBL2 Promotes Tumorigenesis via PRMT5/WDR77-Mediated AKT Activation in Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 11 39499734
2023 WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response. Nature communications 10 37563140
2023 The PRMT5/WDR77 complex restricts hepatitis E virus replication. PLoS pathogens 9 37276230
2021 Sulforaphane inhibits PRMT5 and MEP50 function to suppress the mesothelioma cancer cell phenotype. Molecular carcinogenesis 8 33872411
2024 Inhibition of PRMT5/MEP50 Arginine Methyltransferase Activity Causes Cancer Vulnerability in NDRG2low Adult T-Cell Leukemia/Lymphoma. International journal of molecular sciences 5 38474089
2024 WDR77 in Pan-Cancer: Revealing expression patterns, genetic insights, and functional roles across diverse tumor types, with a spotlight on colorectal cancer. Translational oncology 5 39182364
2023 In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome. RNA (New York, N.Y.) 5 37562960
2013 Functional domains of androgen receptor coactivator p44/Mep50/WDR77and its interaction with Smad1. PloS one 5 23734213
2012 Loss of the androgen receptor cofactor p44/WDR77 induces astrogliosis. Molecular and cellular biology 5 22751923
2025 RNF187 Facilitates Proliferation and Migration of Human Spermatogonial Stem Cells Through WDR77 Polyubiquitination. Cell proliferation 4 40197797
2025 HNRNPC Promotes Keloid Progression by Modulating the Stability of N6-Methyladenosine-Modified WDR77 mRNA and Expression of TGF-β and SMAD3. The Journal of investigative dermatology 4 40484365
2024 PRMT5/WDR77 Enhances the Proliferation of Squamous Cell Carcinoma via the ΔNp63α-p21 Axis. Cancers 4 39594744
2016 Expression of mep50 in adult and embryos of medaka fish (Oryzias latipes). Fish physiology and biochemistry 3 26749004
2025 C6orf223 promotes colorectal cancer growth and metastasis by facilitating PRMT5-MEP50 multiprotein complex assembling. The Journal of clinical investigation 2 41090362
2023 Mep50 is essential for embryonic development in medaka fish. Gene 2 36963734
2022 MafB, WDR77, and ß-catenin interact with each other and have similar genome association profiles. PloS one 2 35482762
2025 The Role of WDR77 in Cancer: More than a PRMT5 Interactor. Molecular cancer research : MCR 1 39853175
2025 Dismantling the epigenetic alliance: Emerging strategies to disrupt the PRMT5:MEP50 complex for cancer therapy. European journal of medicinal chemistry 1 40532498
2025 Genomic features of the methylosome protein MEP50 and its implications in hormone signaling and cancer. Endocrine connections 1 40919714
2025 Disrupting the interaction between androgen receptor and its coregulator WDR77 delays the growth of treatment-resistant prostate cancer. Cell reports 1 40934084
2026 Posttranscriptional regulation of PD-1 by PRMT5/WDR77 complex shapes T cell effector function and antitumor immunity. The Journal of clinical investigation 0 41623183
2025 GATA3 and E2F6 negatively regulate WDR77 expression to inhibit prostate cancer cell growth. Transcription 0 40071854
2025 PRMT5:MEP50 Are Mediators of Treatment-Induced Neuroendocrine Differentiation in Prostate Cancer. The Prostate 0 40677010
2025 Histone-related gene WDR77 promotes tumor progression through cell cycle regulation in skin cutaneous melanoma. Frontiers in immunology 0 41425556
2023 In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome. bioRxiv : the preprint server for biology 0 37215023

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