Affinage

WDR4

tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 · UniProt P57081

Length
412 aa
Mass
45.5 kDa
Annotated
2026-06-11
41 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WDR4 is a non-catalytic WD40-repeat scaffold protein best characterized as the obligate partner of METTL1 in the heterodimeric tRNA methyltransferase that installs the m7G46 modification on a defined subset of tRNAs (PMID:36599982, PMID:36599985, PMID:26416026). Structural studies establish that WDR4 positions both METTL1 and the tRNA T-arm, with the composite protein surface recognizing the tRNA elbow through shape complementarity; the METTL1 N-terminus, partly ordered by WDR4 contact, forms the catalytic centre and acts as a conformational switch coupling SAM binding to methyl transfer, an activity inhibited by S27 phosphorylation (PMID:36599982, PMID:36599985). Efficient methylation requires both the D-stem and T-stem of the tRNA substrate, and the active heterodimer assembles only through co-translational association of the two subunits (PMID:17382321, PMID:18164779). Through this modification, METTL1-WDR4 globally shapes mRNA translation in a codon-usage-dependent manner: loss reduces ribosome transit at cognate codons, impairs translation of mRNAs enriched in m7G-decoded codons, and disrupts embryonic stem cell self-renewal and neural differentiation (PMID:29983320, PMID:34371184). Beyond tRNA, the complex deposits internal m7G marks that stabilize tumor-promoting mRNAs and miRNAs (PMID:38493882, PMID:41663759, PMID:40857569). WDR4 also operates independently of its methyltransferase role: it serves as a substrate adaptor of the CUL4 E3 ubiquitin ligase, directing ubiquitination and proteasomal degradation of PTPN23 to sustain EGFR/c-MET signaling and of Arhgap17 to activate Rac1 and drive neural progenitor proliferation (PMID:37821451, PMID:36681682); and in tumor-associated macrophages it binds eIF4E2 to selectively translate ABCA1 and promote cholesterol efflux (PMID:41315768). A missense mutation in WDR4 that reduces tRNA m7G46 methylation causes a human microcephalic primordial dwarfism, with disease-relevant impairment of ciliogenesis linked to dysregulated protein synthesis and depletion of free ubiquitin pools (PMID:26416026, PMID:39251572).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 Medium

    Established that the WDR4 ortholog is required for normal development in a whole organism, framing it as a five-WD40-repeat protein with developmental rather than purely housekeeping functions.

    Evidence P-element mutagenesis and transgenic rescue in Drosophila showing spermatogenesis arrest and female germline cell-cycle defects

    PMID:16762337

    Open questions at the time
    • Molecular mechanism not defined
    • No link to tRNA modification yet established
    • Phenotype is ortholog-based, not human
  2. 2007 Medium

    Defined the biochemical substrate requirements and assembly logic of the methyltransferase, showing the heterodimer requires intact tRNA D- and T-stem structure and forms an active enzyme only via co-translational subunit association.

    Evidence In vitro methyl-transfer assays with truncated/mutant yeast tRNA(Phe) and wheat-germ co-translation reconstitution

    PMID:17382321 PMID:18164779

    Open questions at the time
    • No structural model of recognition
    • Performed on yeast orthologs only
    • Single-lab in vitro reconstitution
  3. 2015 High

    Linked WDR4 to human disease and confirmed its required role in tRNA m7G46 modification, showing a missense mutation reduces methylation of specific tRNAs.

    Evidence Autozygome/exome analysis of patient families plus tRNA m7G46 assays in patient cells and matched yeast mutants

    PMID:26416026

    Open questions at the time
    • Translational consequences of the hypomorph not measured
    • How loss of m7G causes the clinical phenotype unresolved
  4. 2018 High

    Demonstrated the functional output of WDR4-dependent m7G: it prevents ribosome pausing at cognate codons and is required for stem cell self-renewal and differentiation.

    Evidence CRISPR knockout of Wdr4/Mettl1 in mESCs with m7G MeRIP-seq, TRAC-seq, ribosome profiling, and differentiation assays

    PMID:29983320

    Open questions at the time
    • Specific mRNAs driving phenotype not pinpointed
    • Does not address non-methyltransferase roles
  5. 2016 High

    Identified a methyltransferase-independent role at replication forks, where the WDR4 ortholog binds FEN1 and modulates its nuclease activity, with loss triggering DNA damage signaling.

    Evidence Reciprocal Co-IP, co-localization with PCNA/FEN1, in vitro FEN1 nuclease assays, and knockdown/KO across Drosophila, mouse, and human cells

    PMID:26751069

    Open questions at the time
    • Relationship to the METTL1 tRNA function unclear
    • Whether human WDR4 directly modulates FEN1 in vivo not resolved
  6. 2020 Medium

    Extended the developmental/translational role by showing WDR4 partners with a TRIM-NHL protein to control germline stem cell homeostasis and ribosome biogenesis.

    Evidence Genetic epistasis with Mei-p26 plus Co-IP of WDR4-TRIM32 in human cells and translation reporter assays

    PMID:31941704

    Open questions at the time
    • Direct biochemical mechanism of WDR4-TRIM32 cooperation undefined
    • Largely ortholog-based
  7. 2021 Medium

    Connected the m7G/translation axis to cancer and placed WDR4 downstream of MYC, implicating codon-usage-linked translation and mRNA stability control in tumorigenesis.

    Evidence tRNA/translation profiling with catalytic mutants in lung cancer; ChIP/RIP/mRNA-stability assays defining a MYC/WDR4/CCNB1 axis in HCC

    PMID:34244479 PMID:34371184

    Open questions at the time
    • EIF2A-CCNB1 mechanism is correlative
    • Whether translation defects fully account for tumor phenotypes unresolved
  8. 2023 High

    Resolved the atomic mechanism of the methyltransferase, showing WDR4 scaffolds METTL1 and the tRNA T-arm and that the METTL1 N-terminus is a SAM-coupled conformational switch regulated by S27 phosphorylation.

    Evidence Crystal and cryo-EM structures of METTL1-WDR4(-tRNA) with biochemical and phospho-mimetic mutagenesis (two independent Nature studies)

    PMID:36599982 PMID:36599985

    Open questions at the time
    • Upstream kinase for S27 not identified
    • Structural basis of tRNA subset selectivity not fully mapped
  9. 2023 High

    Established WDR4 as a CUL4 E3 ligase substrate adaptor, revealing a ubiquitination-based, methyltransferase-independent function controlling receptor trafficking and Rac1 signaling.

    Evidence Ubiquitylome MS, Co-IP, ubiquitination/trafficking assays and peptide competition for PTPN23 (NSCLC); conditional KO plus Arhgap17 rescue and Rac1 assays for cerebellar progenitors

    PMID:36681682 PMID:37821451

    Open questions at the time
    • How WDR4 partitions between methyltransferase and ligase-adaptor roles unknown
    • Direct CUL4-WDR4 architecture not structurally defined
  10. 2023 Medium

    Added a nuclear adaptor function, with WDR4 bridging DDX20 and Egr1 to repress ARRB2 transcription in metastatic cancer.

    Evidence Co-IP, nuclear localization and luciferase reporter assays with loss-of-function in bladder cancer cells and in vivo

    PMID:37783676

    Open questions at the time
    • Direct vs indirect bridging not biochemically dissected
    • Single-lab, single-context
  11. 2024 Medium

    Linked WDR4 loss to a microcephaly-relevant cellular defect, showing dysregulated protein synthesis and ubiquitin depletion impair ciliogenesis, rescuable by proteasome inhibition or ubiquitin supply.

    Evidence Patient fibroblasts and zebrafish with proteasome/ubiquitin assays, ciliogenesis readouts, and pharmacological/genetic rescue

    PMID:39251572

    Open questions at the time
    • Mechanistic chain from m7G loss to ubiquitin depletion not fully defined
    • Single lab
  12. 2025 High

    Defined a fully methyltransferase-independent cytoplasmic translational function, with WDR4 binding eIF4E2 to selectively translate ABCA1 and reprogram tumor-associated macrophages.

    Evidence Co-IP, polysome/selective translation profiling, cholesterol efflux assays, and CpG-siRNA WDR4 silencing in TAMs in vivo

    PMID:41315768

    Open questions at the time
    • Structural basis of WDR4-eIF4E2 interaction unknown
    • Selectivity for ABCA1 mRNA unexplained
  13. 2025 Low

    Broadened the m7G-dependent target repertoire to internal mRNA and miRNA sites controlling stress, growth, and drug-resistance pathways.

    Evidence MeRIP-seq with catalytic-mutant rescue defining m7G of SCLT1 mRNA (NF-kB/gefitinib resistance) and let-7 miRNA (TOR-JNK-dMyc); plus adipocyte browning and GSK3beta/beta-catenin reports

    PMID:40009829 PMID:40857569 PMID:41292047 PMID:41663759

    Open questions at the time
    • Adipocyte browning and GSK3beta findings are single-lab/single-model and not independently confirmed
    • Direct vs indirect effects of methylation on each target not always separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How WDR4 is partitioned and regulated among its distinct roles — methyltransferase scaffold, CUL4 ligase adaptor, eIF4E2-associated translation factor, and replication/transcription adaptor — and what determines context-specific function remains unresolved.
  • No unifying regulatory model linking the moonlighting activities
  • Determinants of subcellular partitioning unknown
  • Upstream signals controlling each function undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 2 GO:0045182 translation regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-9609507 Protein localization 1
Partners
ARHGAP17DDX20EIF2AEIF4E2FEN1METTL1PTPN23TRIM32
Complex memberships
CUL4 E3 ubiquitin ligaseMETTL1-WDR4 methyltransferase

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 Crystal structure of METTL1-WDR4 and cryo-EM structures of METTL1-WDR4-tRNA revealed that WDR4 serves as a scaffold for METTL1 and the tRNA T-arm; the composite protein surface recognizes the tRNA elbow through shape complementarity. The METTL1 N terminus couples cofactor (SAM) binding with conformational changes in the tRNA, catalytic loop, and WDR4 C terminus, acting as a switch to activate m7G methylation. S27 phosphorylation of the METTL1 N-terminal region inhibits methyltransferase activity by disrupting the catalytic centre. X-ray crystallography, cryo-EM, biochemical methyltransferase assays, mutagenesis (S27 phosphorylation site), cellular studies Nature High 36599982 36599985
2023 WDR4 serves as a scaffold for METTL1 and the tRNA T-arm. The predicted disordered N-terminal region of METTL1 is part of the catalytic pocket and essential for methyltransferase activity. S27 phosphorylation in the METTL1 N-terminal region inhibits methyltransferase activity by locally disrupting the catalytic centre, providing a phosphorylation-mediated regulatory mechanism for METTL1-WDR4. Cryo-EM structure of METTL1-WDR4-tRNA, crystal structures of METTL1, biochemical methyltransferase assays, phospho-mimetic and phospho-dead mutagenesis, cellular assays Nature High 36599985
2015 WDR4 is the human ortholog of yeast Trm82, an essential non-catalytic component of the Trm8/Trm82 holoenzyme. A missense mutation in WDR4 (and the corresponding yeast mutation) significantly reduces m7G46 methylation of specific tRNA species, establishing WDR4 as required for tRNA m7G46 modification in humans. Autozygome/exome analysis to identify disease mutation; functional validation by measuring m7G46 methylation of tRNA in patient cells and yeast carrying the corresponding mutation Genome biology High 26416026
2018 Mettl1 or Wdr4 knockout in mouse embryonic stem cells (mESCs) reduces m7G tRNA modification at a 'RAGGU' motif in the variable loop of a subset of 22 tRNAs, causes increased ribosome occupancy at corresponding codons (ribosome pausing), impairs mRNA translation globally, and results in defective ESC self-renewal and neural differentiation. m7G MeRIP-seq (methylated tRNA immunoprecipitation sequencing), TRAC-seq (tRNA reduction and cleavage sequencing), ribosome profiling, CRISPR/Cas9 knockout of Mettl1 and Wdr4, differentiation assays Molecular cell High 29983320
2007 The yeast Trm8-Trm82 (ortholog of METTL1-WDR4) complex requires both the D-stem and T-stem structures of tRNA for efficient methyl-transfer to G46. Tertiary base pairs in the D-stem are important but not essential, suggesting they support induced fit of the G46 base into the catalytic pocket. In vitro methyl-transfer activity assays with truncated and mutant yeast tRNA(Phe) transcripts FEBS letters Medium 17382321
2007 Active Trm8-Trm82 (yeast ortholog of METTL1-WDR4) heterodimer is only formed when both subunits are co-translated; mixing individually translated subunits does not produce active enzyme, indicating the association is translationally coupled. Kinetic parameters confirmed comparable activity to other tRNA methyltransferases. Wheat germ cell-free co-translation, in vitro methyltransferase activity assay, two-dimensional TLC and aniline cleavage to confirm m7G46 production Journal of biotechnology Medium 18164779
2016 Drosophila Wuho (WDR4 ortholog) interacts with Flap Endonuclease 1 (FEN1) and localizes to sites of nascent DNA synthesis along with replication proteins FEN1 and PCNA. WH modulates FEN1 endonucleolytic activities in a substrate-dependent manner: it stimulates FEN1 flap endonuclease activity but inhibits gap endonuclease activity. Knockdown of WH in Drosophila, mouse, and human cells causes DNA strand breaks and apoptosis via ATM/Chk2/p53 signaling. Co-immunoprecipitation to identify FEN1 as binding partner; fluorescence microscopy for co-localization with replication proteins; siRNA knockdown in multiple species; FEN1 endonuclease activity assays with purified proteins; mouse knockout (early embryonic lethal with DNA damage) PLoS biology High 26751069
2020 Drosophila Wuho (WDR4 ortholog) interacts epistatically with the TRIM-NHL protein Mei-p26 (human TRIM32 ortholog) to maintain ovarian germline stem cell homeostasis. In germline stem cells, Wh and Mei-p26 promote BMP stemness signaling; in GSC progeny they silence nanos translation, downregulate differentiation-related microRNAs, and suppress ribosomal biogenesis via dMyc. Human WDR4 interacts with TRIM32 in human cells. Genetic epistasis analysis (double mutants), Co-immunoprecipitation (Wh-Mei-p26, WDR4-TRIM32 in human cells), translation reporter assays, signaling pathway readouts Development (Cambridge, England) Medium 31941704
2006 Drosophila Wuho (WDR4 ortholog) is essential for spermatogenesis; wh null mutants arrest spermatogenesis at the elongating spermatid stage. In female wh mutants, cystocytes fail to arrest at the fourth mitotic cycle and do not undergo nurse-cell endoreplication. The WH protein contains five WD40 repeats and a bipartite nuclear localization signal. P-element mutagenesis, rescue experiments with transgenes (wh vs. top3beta), immunostaining, cytological analysis Developmental biology Medium 16762337
2023 WDR4 acts as a substrate adaptor of the CUL4 E3 ubiquitin ligase and mediates ubiquitination and proteasomal degradation of PTPN23 (a component of the ESCRT complex). WDR4-mediated PTPN23 degradation suppresses lysosomal trafficking and degradation of EGFR and c-MET, thereby sustaining their signaling in NSCLC. A competing peptide that blocks PTPN23 binding to WDR4 promotes EGFR/c-MET degradation and inhibits EGFR TKI-resistant NSCLC growth. Unbiased ubiquitylome mass spectrometry, Co-IP, ubiquitination assays, lysosome trafficking assays, peptide competition experiments, in vitro and in vivo proliferation/invasion assays Cell death & disease High 37821451
2023 WDR4 promotes cerebellar granule neuron progenitor (GNP) proliferation by inducing ubiquitination and degradation of Arhgap17, thereby activating Rac1 and facilitating cell cycle progression. Wdr4 deficiency in GNPs reduces cerebellar foliation and impairs Purkinje neuron organization, leading to locomotion defects. Conditional knockout mouse model (Wdr4 in GNPs), ubiquitination assays, Rac1 activity assays, rescue experiments with Arhgap17, immunofluorescence, behavioral locomotion tests Cell death & disease High 36681682
2018 Wuho (WDR4) deficiency in mouse embryonic fibroblasts (MEFs) induces γH2AX elevation (DNA damage), heterochromatin relaxation, p53 activation, caspase-mediated apoptosis, and p21-mediated G2/M cell cycle arrest. Tamoxifen-inducible Cre-mediated conditional knockout MEFs (CAGGCre-ER), western blot for γH2AX, p53, p21, caspase markers, flow cytometry for cell cycle Cellular signalling Medium 29574139
2021 METTL1/WDR4-mediated m7G tRNA modification promotes translation of mRNAs enriched in m7G tRNA-decoded codons (codon usage-linked translation regulation); knockdown of METTL1 decreased translation of such mRNAs, impaired lung cancer cell proliferation, invasion, and tumorigenicity in vitro and in vivo. tRNA methylation profiling, mRNA translation profiling (ribosome footprinting), METTL1 mutagenesis (catalytic mutant), gain- and loss-of-function in lung cancer cell lines, xenograft models Molecular therapy Medium 34371184
2021 WDR4 is transcriptionally activated by c-MYC, and WDR4 promotes CCNB1 mRNA stability and translation in HCC by enhancing binding of EIF2A to CCNB1 mRNA. This defines a MYC/WDR4/CCNB1/PI3K/AKT/P53 signaling axis. ChIP assay for MYC binding to WDR4 promoter, RNA immunoprecipitation for EIF2A-CCNB1 mRNA interaction, mRNA stability assays, Western blot, luciferase reporter, loss-of-function and gain-of-function in HCC cells, xenograft models Cell death & disease Medium 34244479
2023 WDR4 promotes nuclear localization of DDX20 and acts as an adaptor to bridge DDX20 and Egr1, thereby inhibiting Egr1-driven transcriptional expression of ARRB2, promoting bladder cancer lymphatic metastasis and progression. Co-immunoprecipitation (WDR4-DDX20, WDR4-Egr1), nuclear localization assay, luciferase reporter for ARRB2 transcription, loss-of-function assays in bladder cancer cells and in vivo Oncogenesis Medium 37783676
2024 WDR4 modulates m7G modification at internal sites of tumor-promoting mRNAs by forming a WDR4-METTL1 protein complex (confirmed by Co-IP in Huh7 cells). WDR4 knockdown reduces both mRNA and protein levels of METTL1, indirectly reducing the WDR4-METTL1 complex. Co-immunoprecipitation (WDR4-METTL1), m7G-MeRIP-seq, RNA-seq, dot blot, CCK-8, colony formation, xenograft tumor models Cellular signalling Medium 38493882
2025 Cytoplasmic WDR4, independently of m7G tRNA modification, directly interacts with eIF4E2 to enhance eIF4E-mediated selective translation of ABCA1, promoting membrane cholesterol efflux and maintaining pro-tumoral macrophage polarization in HCC-associated tumor-associated macrophages (TAMs). Co-immunoprecipitation (WDR4-eIF4E2), polysome profiling/selective translation assays, cholesterol efflux assays, WDR4 silencing in TAMs via CpG-siRNA delivery, in vivo tumor models Nature cell biology High 41315768
2024 WDR4 loss-of-function is associated with increased protein synthesis, upregulation of proteasomal activity, and reduction of free ubiquitin precursor pools, leading to impaired ciliogenesis. Inhibition of proteasomal activity or supplementation with free ubiquitin restores normal ciliogenesis and ameliorates microcephaly phenotypes. Human fibroblasts, zebrafish embryos, patient-derived cells; proteasome activity assays, ubiquitin pool measurement, cilia formation assays, proteasome inhibitor and ubiquitin supplementation rescue experiments Cell death & disease Medium 39251572
2025 In Drosophila, Wdr4 (WDR4 ortholog) cooperates with Mettl1 to catalyze m7G modification of let-7 miRNA. Loss of Wdr4 or Mettl1 reduces let-7 levels, aberrantly activating TOR-JNK-dMyc signaling, driving elevated ribosome biogenesis, intestinal stem cell overproliferation, and intestinal dysplasia. Expression of human WDR4 and METTL1 (but not catalytic-dead METTL1 mutant) rescues ISC homeostasis. Drosophila genetic loss-of-function, let-7 miRNA modification assays, TOR/JNK pathway readouts, ribosome biogenesis assays, transgenic human WDR4/METTL1 rescue experiments with catalytic-dead mutant controls EMBO reports Medium 41663759
2025 METTL1/WDR4-mediated m7G methylation stabilizes SCLT1 mRNA; knockdown reduces SCLT1 methylation and mRNA stability, while wild-type but not catalytically inactive METTL1 restores stability. METTL1/WDR4-mediated m7G modification of SCLT1 activates the NF-κB signaling pathway to confer gefitinib resistance in NSCLC. m7G MeRIP-seq, RNA-seq, mRNA stability assays, catalytic mutant rescue experiments, NF-κB pathway assays, xenograft models Genomics, proteomics & bioinformatics Medium 40857569
2025 WDR4 overexpression reshapes the tRNA m7G methylome in adipocytes, enhancing translation of BMP8B; BMP8B knockdown partially counteracts WDR4-mediated mitophagy and adipocyte browning, placing WDR4-driven tRNA m7G modification upstream of BMP8B translation in the browning pathway. TRAC-seq, tRNA m7G methylome profiling, BMP8B knockdown rescue, mitophagy markers (LC3, mitochondrial ultrastructure), 3T3-L1 overexpression/knockout experiments Adipocyte Low 41292047
2025 WDR4 interacts with GSK3β (identified by Co-IP-LC/MS) and promotes GSK3β phosphorylation, thereby activating the β-catenin pathway to promote CRC proliferation, migration, and invasion. Co-IP-LC/MS to identify GSK3β binding, western blot for GSK3β phosphorylation, β-catenin pathway readouts, loss-of-function and gain-of-function in CRC cells and xenograft models Biochemistry and cell biology Low 40009829

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Mettl1/Wdr4-Mediated m7G tRNA Methylome Is Required for Normal mRNA Translation and Embryonic Stem Cell Self-Renewal and Differentiation. Molecular cell 379 29983320
2021 METTL1/WDR4-mediated m7G tRNA modifications and m7G codon usage promote mRNA translation and lung cancer progression. Molecular therapy : the journal of the American Society of Gene Therapy 224 34371184
2021 MYC-targeted WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in hepatocellular carcinoma. Cell death & disease 191 34244479
2022 Aberrant translation regulated by METTL1/WDR4-mediated tRNA N7-methylguanosine modification drives head and neck squamous cell carcinoma progression. Cancer communications (London, England) 167 35179319
2015 Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism. Genome biology 157 26416026
2023 Structures and mechanisms of tRNA methylation by METTL1-WDR4. Nature 95 36599982
2023 Structural basis of regulated m7G tRNA modification by METTL1-WDR4. Nature 91 36599985
2022 Novel roles of METTL1/WDR4 in tumor via m7G methylation. Molecular therapy oncolytics 75 35784404
2018 Mutations in WDR4 as a new cause of Galloway-Mowat syndrome. American journal of medical genetics. Part A 75 30079490
2000 Isolation and characterization of a human chromosome 21q22.3 gene (WDR4) and its mouse homologue that code for a WD-repeat protein. Genomics 52 10950928
2017 Further delineation of the phenotype caused by biallelic variants in the WDR4 gene. Clinical genetics 49 28617965
2023 METTL1/WDR4-mediated tRNA m7G modification and mRNA translation control promote oncogenesis and doxorubicin resistance. Oncogene 46 37185458
2024 RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer. Journal of advanced research 31 38960276
2007 RNA recognition mechanism of eukaryote tRNA (m7G46) methyltransferase (Trm8-Trm82 complex). FEBS letters 30 17382321
2023 WDR4/TRIM28 is a novel molecular target linked to lenvatinib resistance that helps retain the stem characteristics in hepatocellular carcinomas. Cancer letters 26 37279851
2016 Wuho Is a New Member in Maintaining Genome Stability through its Interaction with Flap Endonuclease 1. PLoS biology 25 26751069
2006 A new Drosophila gene wh (wuho) with WD40 repeats is essential for spermatogenesis and has maximal expression in hub cells. Developmental biology 21 16762337
2018 Speech and language delay in a patient with WDR4 mutations. European journal of medical genetics 20 29597095
2023 PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target. Cell death & disease 19 37821451
2021 Aberrant expression of WDR4 affects the clinical significance of cancer immunity in pan-cancer. Aging 19 34282052
2020 WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in Drosophila. Development (Cambridge, England) 16 31941704
2007 Production of yeast tRNA (m(7)G46) methyltransferase (Trm8-Trm82 complex) in a wheat germ cell-free translation system. Journal of biotechnology 14 18164779
2024 WDR4 promotes HCC pathogenesis through N7-methylguanosine by regulating and interacting with METTL1. Cellular signalling 13 38493882
2023 Wdr4 promotes cerebellar development and locomotion through Arhgap17-mediated Rac1 activation. Cell death & disease 10 36681682
2022 WDR4 gene polymorphisms increase hepatoblastoma susceptibility in girls. Journal of Cancer 10 36186903
2023 WDR4 gene polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study. Journal of Cancer 8 37283791
2023 WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2. Oncogenesis 7 37783676
2025 Functions of METTL1/WDR4 and QKI as m7G modification - related enzymes in digestive diseases. Frontiers in pharmacology 6 39850560
2021 Genetic Association of the Functional WDR4 Gene in Male Fertility. Journal of personalized medicine 5 34442404
2025 Upregulation of WDR4 mediated by RBFOX2 promotes laryngeal cancer progression through the WDR4/m7G/lncRNA ZFAS1/RBFOX2 axis. Naunyn-Schmiedeberg's archives of pharmacology 3 39774908
2018 Wuho/WDR4 deficiency inhibits cell proliferation and induces apoptosis via DNA damage in mouse embryonic fibroblasts. Cellular signalling 3 29574139
2025 WDR4 drives tumour-associated macrophage reprogramming and tumour progression via selective translation and membrane cholesterol efflux. Nature cell biology 2 41315768
2025 The P300/ETV4-WDR4 axis promotes colorectal cancer progression via m7G-mediated SPP1 mRNA stabilization and autophagy suppression. Cellular signalling 1 40681009
2025 METTL1-WDR4 promotes the migration and proliferation of gastric cancer through N7-methylguanosine. Cellular oncology (Dordrecht, Netherlands) 1 40764449
2025 METTL1/WDR4-mediated m7G Hypermethylation of SCLT1 mRNA Promotes Gefitinib Resistance in NSCLC. Genomics, proteomics & bioinformatics 1 40857569
2025 Mechanistic Insights Into METTL1/WDR4-Mediated m7G Modification in Prostate Cancer Progression and Its Potential as a Therapeutic Target. Journal of biochemical and molecular toxicology 1 41098012
2025 WDR4 promotes glioma progression by regulating cell proliferation and cell cycle via the PI3K/Akt-CDK1/2 signaling pathway. Neoplasma 1 41235531
2024 Cilia defects upon loss of WDR4 are linked to proteasomal hyperactivity and ubiquitin shortage. Cell death & disease 1 39251572
2026 Wdr4 regulates ribosome biogenesis and intestinal homeostasis via let-7. EMBO reports 0 41663759
2025 WDR4 promotes colorectal cancer progression by activating the GSK3β/β-catenin pathway. Biochemistry and cell biology = Biochimie et biologie cellulaire 0 40009829
2025 WDR4-mediate tRNA m7G modification to promote mitophagy and browning of white adipose tissue for ameliorating obesity in male mice. Adipocyte 0 41292047

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