Affinage

WTAP

Pre-mRNA-splicing regulator WTAP · UniProt Q15007

Length
396 aa
Mass
44.2 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WTAP is the principal regulatory subunit of the m6A RNA methyltransferase complex (MTC), where it bridges the METTL3–METTL14 catalytic heterodimer to mRNA substrates in nuclear speckles and is essential for m6A deposition in vivo; in its absence, METTL3 RNA-binding and catalytic activity are severely impaired (PMID:24407421, PMID:29348140). WTAP also undergoes phase separation to concentrate the MTC at nuclear speckles and is recruited via ZC3H13–RBM15 bridging, with its protein stability controlled by ubiquitin-proteasome degradation modulated by ERK1/2 phosphorylation (Ser341), O-GlcNAcylation, and USP7-mediated deubiquitination (PMID:39007267, PMID:35781818, PMID:34312368, PMID:39671515). Beyond m6A, WTAP exerts m6A-independent transcriptional functions by binding gene promoters together with RNA polymerase II and the H3K9ac mark to maintain chromatin accessibility, as demonstrated by cardiomyocyte-specific knockout causing dilated cardiomyopathy not rescued by METTL3 overexpression and hepatocyte-specific knockout derepressing oncogenic signaling (PMID:38224851, PMID:37777158, PMID:35927268). Wtap knockout mice die at E10.5 with failure of mesoderm and endoderm differentiation, and tissue-specific deletions reveal essential roles in spermatogenesis, pancreatic beta-cell function, cerebellar Purkinje cell survival, and inflammatory responses (PMID:18224709, PMID:33053361, PMID:36920524, PMID:35304325, PMID:39007267).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Before WTAP's molecular function was known, the protein was identified as a nuclear speckle-localized partner of the tumor suppressor WT1, establishing it as a nuclear factor associated with splicing factor-rich domains.

    Evidence Yeast two-hybrid, in vitro binding, Co-IP, and immunofluorescence in mammalian cells

    PMID:11001926

    Open questions at the time
    • Functional consequence of WT1–WTAP interaction unknown
    • No link to RNA modification at this stage
  2. 2008 High

    Gene-trap knockout demonstrated that Wtap is essential for early embryogenesis—loss causes lethality by E10.5 with failed mesoderm/endoderm differentiation—establishing WTAP as a developmental necessity before its catalytic context was known.

    Evidence Wtap gene-trap KO mouse with chimera analysis and histology

    PMID:18224709

    Open questions at the time
    • Molecular mechanism of developmental failure unresolved
    • No connection to RNA methylation yet
  3. 2014 High

    The central mechanistic breakthrough: WTAP was identified as a required regulatory subunit of the METTL3–METTL14 m6A methyltransferase complex, essential for nuclear speckle localization, METTL3 RNA-binding, and catalytic activity in vivo, unifying WTAP's nuclear speckle localization with epitranscriptomic function.

    Evidence Reciprocal Co-IP, PAR-CLIP, m6A activity assay, morpholino knockdown in zebrafish

    PMID:24407421

    Open questions at the time
    • Precise binding interface within the complex not yet mapped
    • How WTAP itself recognizes target RNAs unclear
  4. 2015 Medium

    WTAP was shown to be required for Xist-mediated X-chromosome silencing, extending its m6A-dependent function to long noncoding RNA-mediated chromatin regulation.

    Evidence Pooled shRNA screen with super-resolution 3D-SIM co-localization of WTAP and Xist RNA

    PMID:26190105

    Open questions at the time
    • Whether WTAP acts via m6A on Xist or through another mechanism not fully resolved
    • Single-lab shRNA screen
  5. 2018 High

    Biochemical reconstitution mapped WTAP binding surfaces on METTL3/14, identified WTAP phosphorylation sites, and showed ZC3H13 bridges RBM15 to WTAP for RNA targeting, defining the molecular architecture and accessory subunit hierarchy of the m6A writer complex.

    Evidence Recombinant protein mapping, in vitro methylation assays, phospho-site mapping; ZC3H13-Rbm15-Wtap Co-IP and epistasis in Drosophila and mouse

    PMID:29348140 PMID:29535189

    Open questions at the time
    • Full atomic structure of WTAP within the complex not determined
    • Stoichiometry of complex unresolved
  6. 2018 High

    Physiological roles in adipogenesis were established: WTAP promotes cell-cycle progression via cyclin A2 during mitotic clonal expansion, and Wtap heterozygous KO mice resist diet-induced obesity, linking m6A writer function to metabolic regulation.

    Evidence siRNA knockdown, cell cycle analysis, Wtap heterozygous KO mouse with metabolic phenotyping

    PMID:29866655

    Open questions at the time
    • Direct m6A targets driving cyclin A2 regulation not identified
    • Heterozygous rather than conditional KO limits tissue-specific conclusions
  7. 2020 High

    Conditional Wtap deletion in Sertoli cells demonstrated WTAP is essential for the spermatogonial stem cell niche, revealing WTAP-dependent m6A governs alternative splicing and translation of niche factor transcripts.

    Evidence Conditional KO mouse with m6A-seq, RNA-seq, and ribosome-nascent-chain complex sequencing

    PMID:33053361

    Open questions at the time
    • Specific m6A reader(s) mediating splicing vs. translation effects not delineated
  8. 2021 Medium

    Multiple studies revealed that WTAP protein stability is actively regulated by signaling cascades: ERK1/2 phosphorylation at Ser341 stabilizes WTAP, while IFN-I signaling promotes its ubiquitin-proteasomal degradation, establishing WTAP turnover as a rheostat for global m6A levels.

    Evidence Phospho-site mapping, protein stability assays, ubiquitination assays, m6A-seq of downstream targets

    PMID:34312368 PMID:34467630

    Open questions at the time
    • E3 ubiquitin ligase(s) targeting WTAP not identified in these studies
    • Whether Ser341 phosphorylation and IFN-I degradation are linked pathways is unknown
  9. 2022 High

    WTAP was shown to have m6A-independent transcriptional regulatory functions: hepatocyte-specific KO revealed WTAP binds DNA motifs in promoters with HDAC1 to suppress gene expression, and CDK9 phosphorylation shuttles WTAP to the cytoplasm in NASH, redefining WTAP as a dual-function nuclear factor.

    Evidence Hepatocyte-specific Wtap KO mouse, ChIP-seq, DNA motif analysis, CDK9 phosphorylation assay, HDAC1 Co-IP

    PMID:35927268

    Open questions at the time
    • DNA-binding domain or motif on WTAP not identified
    • Relationship between WTAP's chromatin function and its m6A function unclear
  10. 2022 Medium

    Additional post-translational control was uncovered: PGE2-EP3 signaling stabilizes WTAP by relieving PKA-mediated ERK1/2 inhibition, and later O-GlcNAcylation plus USP7 deubiquitination were shown to cooperatively stabilize WTAP, demonstrating multiple converging PTM inputs on WTAP homeostasis.

    Evidence EP3 KO mouse, ubiquitination assays, mass spectrometry of O-GlcNAc sites, USP7 knockdown/overexpression

    PMID:35781818 PMID:39671515

    Open questions at the time
    • Quantitative contribution of each PTM to WTAP half-life not determined
    • Crosstalk among phosphorylation, O-GlcNAc, and ubiquitination on WTAP uncharacterized
  11. 2023 High

    Cardiomyocyte-specific Wtap KO proved WTAP has an m6A-independent role in cardiac gene regulation: WTAP directly binds Mef2c promoter and maintains chromatin accessibility at cardiac transcription factor loci, and the phenotype is not rescued by METTL3 overexpression, definitively separating WTAP's transcriptional from its epitranscriptomic functions.

    Evidence Cardiomyocyte-specific KO mouse, promoter luciferase, ATAC-seq, Mettl3 overexpression rescue

    PMID:38224851

    Open questions at the time
    • Whether WTAP's transcriptional function requires a distinct protein domain is unknown
    • Chromatin co-factors beyond H3K9ac and RNA Pol II not identified
  12. 2023 Medium

    A cleaved METTL3 isoform (METTL3a) was shown to mediate METTL3 homodimerization required for WTAP recruitment, refining the assembly hierarchy of the m6A writer complex.

    Evidence Co-IP with METTL3a deletion mutants and m6A-seq

    PMID:37589705

    Open questions at the time
    • Protease responsible for METTL3 cleavage not identified
    • Structural basis of METTL3a-dependent WTAP recruitment unknown
  13. 2024 High

    WTAP was shown to undergo liquid-liquid phase separation that concentrates the m6A writer complex at nuclear speckles; NF-κB/p65 transcriptionally upregulates WTAP during inflammation, and myeloid-specific WTAP deletion attenuates sepsis and colitis, connecting WTAP phase behavior to innate immune m6A regulation.

    Evidence Phase separation assay, ChIP for p65 at WTAP promoter, myeloid-specific KO mouse in LPS-sepsis and DSS-IBD models, m6A-seq

    PMID:39007267

    Open questions at the time
    • Intrinsically disordered regions driving WTAP phase separation not mapped
    • Whether phase separation is required vs. correlative for speckle localization unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of WTAP within the complete m6A writer complex, the identity of the E3 ligase(s) responsible for WTAP ubiquitination, the molecular determinant enabling WTAP's direct promoter DNA binding, and how cells coordinate WTAP's m6A-dependent and m6A-independent functions in the same nucleus.
  • No high-resolution structure of WTAP in the MTC
  • E3 ubiquitin ligase(s) for WTAP degradation not identified
  • DNA-binding domain/motif on WTAP protein not characterized
  • Switch mechanism between m6A-dependent and transcriptional roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005654 nucleoplasm 4 GO:0005634 nucleus 3
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
DGCR8HDAC1METTL14METTL3RBM15USP7WT1ZC3H13
Complex memberships
METTL3-METTL14-WTAP m6A methyltransferase complexZC3H13-RBM15-WTAP bridging complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 WTAP is a regulatory subunit of the m6A methyltransferase complex: it interacts with METTL3 and METTL14, is required for their localization to nuclear speckles, and is essential for catalytic m6A methyltransferase activity in vivo. In the absence of WTAP, RNA-binding capability of METTL3 is strongly reduced, suggesting WTAP recruits the complex to mRNA targets. Co-immunoprecipitation, PAR-CLIP, nuclear speckle localization assay, m6A methyltransferase activity assay, morpholino knockdown in zebrafish Cell research High 24407421
2000 WTAP was identified as a WT1-associating protein; it physically interacts with WT1 both in vitro and in vivo, localizes to the nucleus including speckles where it co-localizes with splicing factors. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, FISH, immunofluorescence localization Human molecular genetics High 11001926
2018 Zc3h13/Flacc bridges the mRNA-binding factor Rbm15/Nito to the m6A machinery component Wtap/Fl(2)d, thereby promoting m6A deposition; disruption of this bridge reduces m6A levels. Co-immunoprecipitation, m6A quantification, genetic knockdown in Drosophila and mice Genes & development High 29535189
2018 Recombinant protein mapping defined the binding surfaces within the METTL3/14-WTAP complex; WTAP is required for the distinct nuclear speckle localization pattern; nuclear localization signals were identified; phosphorylation sites on endogenous WTAP were mapped; METTL14 C-terminal RGG repeats contribute to RNA substrate binding for m6A activity. Recombinant protein binding assays, in vitro methylation assay, phosphorylation site mapping, nuclear localization signal mutagenesis RNA (New York, N.Y.) High 29348140
2015 WTAP, identified via shRNA screen, is required for the establishment of Xist-mediated X-chromosome silencing and co-localizes with Xist RNA within the nuclear matrix subcompartment as demonstrated by super-resolution 3D-SIM microscopy. Pooled shRNA screen, validation knockdown, super-resolution 3D-SIM microscopy co-localization Cell reports Medium 26190105
2008 Wtap knockout mice die by E10.5 with defective egg-cylinder formation; Wtap is required for differentiation of endoderm and mesoderm; chimera analysis showed Wtap in extraembryonic tissues is required for mesoderm and endoderm formation in embryonic tissues. Gene-trap mouse knockout, chimera analysis, histological analysis of embryos and ES cells Developmental dynamics High 18224709
2018 The WTAP-METTL3-METTL14 complex positively controls adipogenesis by promoting cell cycle transition in mitotic clonal expansion (MCE); WTAP knockdown causes cell cycle arrest and suppression of cyclin A2 upregulation; Wtap heterozygous knockout mice are protected from diet-induced obesity. siRNA knockdown, cell cycle analysis, heterozygous Wtap KO mouse model with metabolic phenotyping Molecular and cellular biology High 29866655
2018 METTL3 levels are critical for WTAP protein homeostasis: both knockdown and overexpression of METTL3 result in WTAP protein upregulation; WTAP upregulation is not sufficient to promote cell proliferation in the absence of functional METTL3, indicating the oncogenic function of WTAP is strictly connected to a functional m6A methylation complex. siRNA/shRNA knockdown, METTL3 overexpression, western blot, cell proliferation assay Cell death & disease Medium 30038300
2019 WTAP-mediated m6A modification of ETS1 mRNA leads to post-transcriptional suppression of ETS1 with HuR as an RNA stabilizer; WTAP modulates G2/M phase via a p21/p27-dependent pattern mediated through ETS1. m6A dot blot, MeRIP assay, RIP assay, dual luciferase reporter assay, ChIP assay, RNA-seq Molecular cancer Medium 31438961
2020 WTAP function in Sertoli cells is essential for sustaining the spermatogonial stem cell niche; conditional Wtap deletion in Sertoli cells causes sterility and progressive loss of SSC population; WTAP regulates alternative splicing events and translation of SSC niche factor transcripts. Conditional knockout mouse, m6A-seq, RNA-seq, ribosome nascent-chain complex-bound mRNA sequencing Stem cell reports High 33053361
2021 circ0008399 binds WTAP to promote formation of the WTAP/METTL3/METTL14 m6A methyltransferase complex and increases TNFAIP3 mRNA stability in an m6A-dependent manner, reducing cisplatin sensitivity in bladder cancer. RNA pulldown, Co-IP, m6A methylation assay, MeRIP assay, functional rescue experiments Cancer research Medium 34702726
2021 WTAP-mediated m6A modification of DIAPH1-AS1 lncRNA enhances its stability via IGF2BP2-dependent pathway; DIAPH1-AS1 acts as molecular adaptor promoting MTDH-LASP1 complex formation, facilitating NPC growth and metastasis. MeRIP-seq, MeRIP-qPCR, RNA stability assay, RIP assay, Co-IP Cell death and differentiation Medium 34999731
2022 WTAP deficiency in islet beta cells decreases METTL3 protein levels and reduces m6A mRNA modification and expression of islet beta cell-specific transcription factors and insulin secretion-related genes; beta cell-specific Mettl3 overexpression partially reverses Wtap-betaKO abnormalities, placing WTAP upstream of METTL3 in beta cell function. Beta cell-specific Wtap KO mouse, Mettl3 overexpression rescue, RNA-seq, MeRIP-seq, metabolic phenotyping Diabetologia High 36920524
2022 HCV infection induces cytoplasmic localization of WTAP; WTAP is required for METTL3 interaction with HCV RNA and for m6A modification of viral RNA; WTAP regulation of HCV RNA m6A modification and virion production is independent of its nuclear localization, demonstrating a cytoplasmic targeting function. Immunofluorescence localization, RIP assay, m6A-seq of viral RNA, siRNA knockdown, virion production assay Journal of virology Medium 36314819
2021 WTAP is degraded via the ubiquitination-proteasome pathway upon activation of IFN-I signaling; WTAP degradation reduces m6A levels on IRF3 and IFNAR1 mRNAs, leading to translational suppression of IRF3 and instability of IFNAR1 mRNA, establishing a negative feedback axis in IFN-I signaling. Ubiquitination assay, proteasome inhibitor treatment, m6A-seq, protein stability assay, IFN signaling assays EMBO reports Medium 34467630
2022 WTAP deficiency in hepatocytes leads to NASH via increased lipolysis in white adipose tissue, enhanced hepatic free fatty acid uptake, and inflammation mediated by IGFBP1, CD36, and CCL2; WTAP binds specific DNA motifs in promoters and suppresses gene expression with involvement of HDAC1; CDK9-mediated phosphorylation causes WTAP translocation from nucleus to cytosol in NASH. Hepatocyte-specific Wtap KO mouse, ChIP-seq, DNA motif binding assay, CDK9 phosphorylation assay, HDAC1 co-IP, fractionation Nature communications High 35927268
2023 WTAP cardiomyocyte-specific KO induces dilated cardiomyopathy and neonatal death; WTAP directly binds to the Mef2c gene promoter and increases its promoter luciferase activity; WTAP deficiency decreases chromatin accessibility at Mef2a and Mef2c promoters, reducing expression of their target genes; the cardiac phenotype is not rescued by Mettl3 overexpression, indicating an m6A-independent transcriptional mechanism. Cardiomyocyte-specific Wtap KO mouse, luciferase reporter assay, ATAC-seq (chromatin accessibility), Mettl3 overexpression rescue experiment Journal of molecular and cellular cardiology High 38224851
2022 WTAP interacts with DGCR8 and accelerates maturation of pri-miR-29b-3p in an m6A-dependent manner; WTAP-mediated m6A modification promotes osteogenic and inhibits adipogenic differentiation of BMSCs through the miR-29b-3p/HDAC4 axis. Co-IP, RIP, MeRIP, RNA pulldown, dual-luciferase assay, in vivo BMSC transplantation Stem cells translational medicine Medium 37010483
2022 WTAP-mediated m6A modification promotes maturation of pri-miR-181a/c to miR-181a/c via YTHDC1 recognition; mature miR-181a/c inhibit SFRP1 mRNA expression, promoting osteogenic differentiation of BMSCs via the WTAP/YTHDC1/miR-181a and miR-181c/SFRP1 axis. Co-IP, RIP, MeRIP, RNA pulldown, dual-luciferase assay Cell death & disease Medium 36650131
2023 PRMT1 methylates WTAP protein, and this modification promotes m6A methylation of NDUFS6 mRNA by the WTAP-containing complex, activating oxidative phosphorylation in multiple myeloma. Co-IP, MS identification of methylation site, MeRIP-seq, PRMT1 knockdown/overexpression, OXPHOS assay Cell death & disease Medium 37558663
2022 PGE2-EP3 axis prevents ubiquitin-mediated proteasomal degradation of WTAP by eliminating PKA-mediated ERK1/2 inhibition; stabilized WTAP promotes Zfp410 mRNA m6A modification to enhance brown adipogenesis. EP3 KO mouse, ubiquitination assay, PKA/ERK1/2 signaling assay, WTAP stability assay, MeRIP-qPCR The EMBO journal Medium 35781818
2021 ERK1/2 signaling phosphorylates WTAP at serine341 and stabilizes WTAP protein; stabilized WTAP promotes m6A methylation of ENO1 mRNA to enhance glycolytic activity in breast cancer. ERK1/2 signaling assay, phospho-site mapping (S341), WTAP protein stability assay, MeRIP-qPCR, cell glycolysis assay Cell death & disease Medium 34312368
2022 Purkinje cell-specific WTAP knockout causes ataxia and cerebellar degeneration; loss of Wtap decreases METTL3/14 expression and reduces m6A methylation in Purkinje cells, leading to PC degeneration and synaptic loss. Conditional KO mouse, immunofluorescence, m6A quantification, western blot, behavioral assay Journal of genetics and genomics Medium 35304325
2023 A cleaved form of METTL3 (METTL3a, residues 239-580) is required for the METTL3-METTL3 homodimerization that is a prerequisite for WTAP recruitment into the m6A methyltransferase complex (MTC); depletion of METTL3a globally disrupts m6A deposition and disrupts METTL3-WTAP interaction. Co-IP, m6A-seq, METTL3a deletion/mutagenesis, cell proliferation assay eLife Medium 37589705
2024 p65 transcriptionally regulates WTAP expression; upregulated WTAP undergoes phase separation to facilitate aggregation of the m6A writer complex to nuclear speckles and deposition of m6A marks on inflammatory transcripts; myeloid-specific WTAP deficiency attenuates LPS-induced sepsis and DSS-induced IBD severity. ChIP assay for p65 at WTAP promoter, phase separation assay, myeloid-specific KO mouse, LPS sepsis and DSS-IBD mouse models, m6A-seq The Journal of clinical investigation High 39007267
2023 O-GlcNAcylation by OGT and de-ubiquitination by USP7 synergistically stabilize WTAP protein; stabilized WTAP promotes LOXL2 m6A modification to enhance mRNA stability via IGF2BP2, leading to secreted LOXL2 activating integrin α5β1-FAK-ERK signaling in glioblastoma stem cells. Mass spectrometry, RIP, Co-IP, OGT/USP7 knockdown/overexpression, m6A-seq, in vitro and in vivo functional assays Neuro-oncology Medium 39671515
2014 The Drosophila WTAP homolog Fl(2)d forms a biochemical complex with the SIX family transcription factor Sine Oculis (So) and is required for normal retinal development; loss-of-function increases Elav and Lozenge levels behind the morphogenetic furrow. Yeast two-hybrid, Co-IP from Kc167 cells, Drosophila genetic loss-of-function analysis Developmental biology Medium 24690230
2022 WTAP-mediated m6A modification of NORAD lncRNA enhances its YTHDF2-dependent decay in senescent nucleus pulposus cells; reduced NORAD releases PUMILIO proteins whose augmented activity represses E2F3 mRNA expression, promoting cellular senescence and intervertebral disc degeneration. m6A-seq, MeRIP-qPCR, siRNA knockdown, gain/loss-of-function, PUMILIO sequestration assay Nature communications Medium 35304463
2021 WTAP promotes m6A methylation of NLRP3 mRNA that is stabilized by IGF2BP1, upregulating NLRP3 inflammasome activation and cell pyroptosis; histone acetyltransferase p300 regulates WTAP expression. m6A-MeRIP assay, RIP assay, shRNA knockdown, WTAP overexpression, p300 inhibitor treatment, in vivo db/db mouse model Cellular & molecular biology letters Medium 35761192
2023 Hepatic deletion of Wtap promotes HCC by decreasing expression of proteasome subunits PSMB4/PSMB6, increasing GRB2 and ERK1/2 protein stability, and activating ERK signaling; WTAP interacts with RNA polymerase II and H3K9ac to maintain transcription of proteasome-related genes. Hepatocyte-specific Wtap KO mouse, ChIP assay (RNA Pol II, H3K9ac), proteasome activity assay, GRB2/ERK stability measurement, PSMB4/6 rescue experiment The Journal of biological chemistry Medium 37777158
2023 WTAP-mediated m6A modification of FOXO1 mRNA in the CDS region enhances Foxo1 mRNA expression and promotes regulatory T cell differentiation and function, contributing to immune tolerance post kidney transplantation. MeRIP-qPCR (CDS region), m6A demethylase overexpression rescue, Treg differentiation assay, in vivo allograft mouse model Laboratory investigation Medium 35864150

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell research 1942 24407421
2019 WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1. Molecular cancer 522 31438961
2018 Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d. Genes & development 507 29535189
2018 Interactions, localization, and phosphorylation of the m6A generating METTL3-METTL14-WTAP complex. RNA (New York, N.Y.) 376 29348140
2015 A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing. Cell reports 227 26190105
2000 Identification of WTAP, a novel Wilms' tumour 1-associating protein. Human molecular genetics 188 11001926
2019 Discovery of Small Molecules that Activate RNA Methylation through Cooperative Binding to the METTL3-14-WTAP Complex Active Site. Cell reports 156 30917327
2021 Circ0008399 Interaction with WTAP Promotes Assembly and Activity of the m6A Methyltransferase Complex and Promotes Cisplatin Resistance in Bladder Cancer. Cancer research 148 34702726
2022 WTAP-mediated m6A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis. Cell death and differentiation 141 34999731
2022 WTAP-mediated m6A modification of lncRNA NORAD promotes intervertebral disc degeneration. Nature communications 137 35304463
2018 The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis. Molecular and cellular biology 132 29866655
2007 The Arabidopsis MUM2 gene encodes a beta-galactosidase required for the production of seed coat mucilage with correct hydration properties. The Plant cell 131 18165329
2018 METTL3 regulates WTAP protein homeostasis. Cell death & disease 121 30038300
2020 WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner. Cell death & disease 113 32814762
2022 WTAP-mediated N6-methyladenosine modification of NLRP3 mRNA in kidney injury of diabetic nephropathy. Cellular & molecular biology letters 109 35761192
2022 The RNA m6A writer WTAP in diseases: structure, roles, and mechanisms. Cell death & disease 109 36207306
2020 N6-methyladenosine (m6A) methyltransferase WTAP accelerates the Warburg effect of gastric cancer through regulating HK2 stability. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 99 33378974
2021 C5aR1-positive neutrophils promote breast cancer glycolysis through WTAP-dependent m6A methylation of ENO1. Cell death & disease 83 34312368
2013 WTAP regulates migration and invasion of cholangiocarcinoma cells. Journal of gastroenterology 79 23354623
2021 N -methyladenosine-Mediated Upregulation of WTAPP1 Promotes WTAP Translation and Wnt Signaling to Facilitate Pancreatic Cancer Progression. Cancer research 75 34362795
2020 METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP. Cell biology international 65 32869897
2023 WTAP-mediated m6A modification modulates bone marrow mesenchymal stem cells differentiation potential and osteoporosis. Cell death & disease 59 36650131
2023 m6A writer WTAP targets NRF2 to accelerate bladder cancer malignancy via m6A-dependent ferroptosis regulation. Apoptosis : an international journal on programmed cell death 59 36719469
2022 circPDE5A regulates prostate cancer metastasis via controlling WTAP-dependent N6-methyladenisine methylation of EIF3C mRNA. Journal of experimental & clinical cancer research : CR 58 35650605
2024 WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury. International journal of surgery (London, England) 47 38874470
2008 Wtap is required for differentiation of endoderm and mesoderm in the mouse embryo. Developmental dynamics : an official publication of the American Association of Anatomists 47 18224709
2022 Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential. Biomolecules 46 36139062
2020 WTAP Function in Sertoli Cells Is Essential for Sustaining the Spermatogonial Stem Cell Niche. Stem cell reports 43 33053361
2021 Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis. Aging 42 34081626
2021 LINC00839/miR-144-3p/WTAP (WT1 Associated protein) axis is involved in regulating hepatocellular carcinoma progression. Bioengineered 42 34634995
2020 LncRNA PCGEM1 accelerates non-small cell lung cancer progression via sponging miR-433-3p to upregulate WTAP. BMC pulmonary medicine 41 32787827
2023 PRMT1 methylation of WTAP promotes multiple myeloma tumorigenesis by activating oxidative phosphorylation via m6A modification of NDUFS6. Cell death & disease 40 37558663
2022 HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner. Journal of immunology research 40 35733918
2021 N6-methyladenosine (m6A)-mediated lncRNA DLGAP1-AS1enhances breast canceradriamycin resistance through miR-299-3p/WTAP feedback loop. Bioengineered 39 34866525
2022 Deficiency of WTAP in hepatocytes induces lipoatrophy and non-alcoholic steatohepatitis (NASH). Nature communications 38 35927268
2022 WTAP Targets the METTL3 m6A-Methyltransferase Complex to Cytoplasmic Hepatitis C Virus RNA to Regulate Infection. Journal of virology 36 36314819
2021 Degradation of WTAP blocks antiviral responses by reducing the m6 A levels of IRF3 and IFNAR1 mRNA. EMBO reports 35 34467630
2022 NRP1 contributes to stemness and potentiates radioresistance via WTAP-mediated m6A methylation of Bcl-2 mRNA in breast cancer. Apoptosis : an international journal on programmed cell death 34 36333630
2021 miR-139-5p Loss-Mediated WTAP Activation Contributes to Hepatocellular Carcinoma Progression by Promoting the Epithelial to Mesenchymal Transition. Frontiers in oncology 33 33937023
2024 WTAP-mediated m6A modification of FRZB triggers the inflammatory response via the Wnt signaling pathway in osteoarthritis. Experimental & molecular medicine 32 38172596
2001 The Saccharomyces cerevisiae MUM2 gene interacts with the DNA replication machinery and is required for meiotic levels of double strand breaks. Genetics 32 11238403
2024 WTAP weakens oxaliplatin chemosensitivity of colorectal cancer by preventing PANoptosis. Cancer letters 31 39270768
2022 PGE2 -EP3 axis promotes brown adipose tissue formation through stabilization of WTAP RNA methyltransferase. The EMBO journal 31 35781818
2006 Structure of the Bet3-Tpc6B core of TRAPP: two Tpc6 paralogs form trimeric complexes with Bet3 and Mum2. Journal of molecular biology 30 16828797
2024 piR-27222 mediates PM2.5-induced lung cancer by resisting cell PANoptosis through the WTAP/m6A axis. Environment international 29 39106633
2023 Deficiency of WTAP in islet beta cells results in beta cell failure and diabetes in mice. Diabetologia 29 36920524
2023 WTAP Mediates NUPR1 Regulation of LCN2 Through m6A Modification to Influence Ferroptosis, Thereby Promoting Breast Cancer Proliferation, Migration and Invasion. Biochemical genetics 29 37477758
2024 Elevated WTAP promotes hyperinflammation by increasing m6A modification in inflammatory disease models. The Journal of clinical investigation 28 39007267
2023 N6-methyladenosine (m6A) methyltransferase WTAP-mediated miR-92b-5p accelerates osteoarthritis progression. Cell communication and signaling : CCS 28 37563688
2023 WTAP boosts lipid oxidation and induces diabetic cardiac fibrosis by enhancing AR methylation. iScience 28 37810250
2021 MicroRNA-501-3p inhibits the proliferation of kidney cancer cells by targeting WTAP. Cancer medicine 28 34595849
2023 m6A methyltransferase WTAP regulates myocardial ischemia reperfusion injury through YTHDF1/FOXO3a signaling. Apoptosis : an international journal on programmed cell death 27 36894806
2024 WTAP/IGF2BP3 mediated m6A modification of the EGR1/PTEN axis regulates the malignant phenotypes of endometrial cancer stem cells. Journal of experimental & clinical cancer research : CR 26 39044249
2021 HIV Replication Is Increased by RNA Methylation METTL3/METTL14/WTAP Complex Activators. ACS omega 26 34179640
2023 Lactoferrin suppresses the progression of colon cancer under hyperglycemia by targeting WTAP/m6A/NT5DC3/HKDC1 axis. Journal of translational medicine 25 36855062
2023 WTAP-Mediated m6A RNA Methylation Regulates the Differentiation of Bone Marrow Mesenchymal Stem Cells via the miR-29b-3p/HDAC4 Axis. Stem cells translational medicine 25 37010483
2022 N6-methyladenosine methyltransferase WTAP-stabilized FOXD2-AS1 promotes the osteosarcoma progression through m6A/FOXM1 axis. Bioengineered 25 35356854
2022 Plumbagin rescues the granulosa cell's pyroptosis by reducing WTAP-mediated N6-methylation in polycystic ovary syndrome. Journal of ovarian research 23 36463191
2024 Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer. Cell death & disease 22 38286802
2023 HIF1α-mediated transactivation of WTAP promotes AML cell proliferation via m6A-dependent stabilization of KDM4B mRNA. Leukemia 22 37087529
2023 Tumor-associated macrophages promote cisplatin resistance in ovarian cancer cells by enhancing WTAP-mediated N6-methyladenosine RNA methylation via the CXCL16/CXCR6 axis. Cancer chemotherapy and pharmacology 22 37272931
2022 Upregulated WTAP expression appears to both promote breast cancer growth and inhibit lymph node metastasis. Scientific reports 22 35046505
2022 WTAP dysregulation-mediated HMGN3-m6A modification inhibited trophoblast invasion in early-onset preeclampsia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 36412513
2023 WTAP promotes macrophage recruitment and increases VEGF secretion via N6-methyladenosine modification in corneal neovascularization. Biochimica et biophysica acta. Molecular basis of disease 20 37019244
2022 TTC22 promotes m6A-mediated WTAP expression and colon cancer metastasis in an RPL4 binding-dependent pattern. Oncogene 20 35798874
2021 ARRB2 promotes colorectal cancer growth through triggering WTAP. Acta biochimica et biophysica Sinica 20 33367479
2021 N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) mitigates the liver fibrosis via WTAP/m6A/Ptch1 axis through Hedgehog pathway. Gene 19 34921949
2014 The Drosophila Wilms׳ Tumor 1-Associating Protein (WTAP) homolog is required for eye development. Developmental biology 19 24690230
2023 The Emerging, Multifaceted Role of WTAP in Cancer and Cancer Therapeutics. Cancers 18 37297015
2023 A cleaved METTL3 potentiates the METTL3-WTAP interaction and breast cancer progression. eLife 18 37589705
2022 SNHG10/miR-141-3p/WTAP axis promotes osteosarcoma proliferation and migration. Journal of biochemical and molecular toxicology 18 35274397
2024 Downregulation of Wtap causes dilated cardiomyopathy and heart failure. Journal of molecular and cellular cardiology 17 38224851
2022 The N6-methyladenosine writer WTAP contributes to the induction of immune tolerance post kidney transplantation by targeting regulatory T cells. Laboratory investigation; a journal of technical methods and pathology 17 35864150
2025 O-GlcNAcylation stabilized WTAP promotes GBM malignant progression in an N6-methyladenosine-dependent manner. Neuro-oncology 16 39671515
2024 WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8. International journal of biological sciences 16 38481803
2024 WTAP/YTHDF1-mediated m6A modification amplifies IFN-γ-induced immunosuppressive properties of human MSCs. Journal of advanced research 16 38944238
2022 WTAP mediates FOXP3 mRNA stability to promote SMARCE1 expression and augment glycolysis in colon adenocarcinoma. Mammalian genome : official journal of the International Mammalian Genome Society 16 36173464
2021 Loss of WTAP Impairs Early Parthenogenetic Embryo Development. Animals : an open access journal from MDPI 16 34199793
2021 Bone Marrow Mesenchymal Stem Cells-Derived Exosomal miR-425-5p Inhibits Acute Myeloid Leukemia Cell Proliferation, Apoptosis, Invasion and Migration by Targeting WTAP. OncoTargets and therapy 16 34594112
2024 WTAP-induced N6-methyladenosine of PD-L1 blocked T-cell-mediated antitumor activity under hypoxia in colorectal cancer. Cancer science 15 38508217
2024 Exosome-based WTAP siRNA delivery ameliorates myocardial ischemia-reperfusion injury. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 14 38367759
2022 ING2-WTAP is a potential therapeutic target in non-small cell lung cancer. Biochemical and biophysical research communications 14 35306362
2022 Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis. Frontiers in immunology 14 36569923
2021 EBV downregulates the m6A "writer" WTAP in EBV-associated gastric carcinoma. Virus research 14 34329695
2024 WTAP/IGF2BP3-mediated GBE1 expression accelerates the proliferation and enhances stemness in pancreatic cancer cells via upregulating c-Myc. Cellular & molecular biology letters 13 38961325
2023 WTAP Mediated the N6-methyladenosine Modification of PDK4 to Regulate the Malignant Behaviors of Colorectal Cancer Cells In Vitro and In Vivo. Current medicinal chemistry 13 36154586
2022 Loss of Wtap results in cerebellar ataxia and degeneration of Purkinje cells. Journal of genetics and genomics = Yi chuan xue bao 13 35304325
2021 Associations between WTAP gene polymorphisms and neuroblastoma susceptibility in Chinese children. Translational pediatrics 13 33633946
2020 The contribution of WTAP gene variants to Wilms tumor susceptibility. Gene 13 32504654
2012 Low bending loss and effectively single-mode all-solid photonic bandgap fiber with an effective area of 650 μm2. Optics letters 13 22513663
2025 WTAP Mediated m6A Modification Stabilizes PDIA3P1 and Promotes Tumor Progression Driven by Histone Lactylation in Esophageal Squamous Cell Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 40470706
2024 Marrow mesenchymal stem cell mediates diabetic nephropathy progression via modulation of Smad2/3/WTAP/m6A/ENO1 axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 38847786
2024 WTAP-mediated m6A modification of TRIM22 promotes diabetic nephropathy by inducing mitochondrial dysfunction via ubiquitination of OPA1. Redox report : communications in free radical research 12 39314036
2022 Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation. PloS one 12 35143566
2003 Exclusion of WTAP and HOXA13 as candidate genes for isolated hypospadias. Scandinavian journal of urology and nephrology 11 14675924
2024 The lncRNAMALAT1-WTAP axis: a novel layer of EMT regulation in hypoxic triple-negative breast cancer. Cell death discovery 10 38862471
2023 Hepatocyte-specific Wtap deficiency promotes hepatocellular carcinoma by activating GRB2-ERK depending on downregulation of proteasome-related genes. The Journal of biological chemistry 10 37777158
2024 Abnormal stress promotes intervertebral disc degeneration through WTAP/YTHDF2-dependent TIMP3 m6A modification. Journal of cellular physiology 9 38345407
2023 AGAP2-AS1 promotes the assembly of m6A methyltransferases and activation of the IL6/STAT3 pathway by binding with WTAP in the carcinogenesis of gastric cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 37983949
2022 A potential biomarker of esophageal squamous cell carcinoma WTAP promotes the proliferation and migration of ESCC. Pathology, research and practice 9 36095919