Ask about this productRelated genes to: WTAP antibody
- Gene:
- WTAP NIH gene
- Name:
- WT1 associated protein
- Previous symbol:
- -
- Synonyms:
- KIAA0105, MGC3925, Mum2
- Chromosome:
- 6q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-19
- Date modifiied:
- 2017-02-28
Related products to: WTAP antibody
Related articles to: WTAP antibody
- - Source: PubMed
Publication date: 2026/06/24
Bao JingSun RuiPan ZhenjiangWei Shepeng - IFNG (interferon gamma)-activated macrophages contribute to accelerated clearance of platelets and excessive secretion of inflammatory cytokines in immune thrombocytopenia (ITP). In this study, we identified two distinct subpopulations of activated macrophages: phagocytic macrophages (M[IFNG]), which predominantly exhibit phagocytic activity, and inflammatory macrophages (M[IFNG]), characterized by their pro-inflammatory capacity. The M(IFNG) and M(IFNG) subsets were functionally disturbed in patients with ITP. Chaperone-mediated autophagy (CMA) deficiency in macrophages was discovered in ITP and has been reported to induce sustained inflammation. Furthermore, CMA interference enhanced pro-inflammatory function rather than phagocytic activity of macrophages . In parallel, macrophage-specific conditional (lysosome associated membrane protein 2A) knockout mice exhibited expansion and excessive cytokine release of M(IFNG). Restoring CMA restrains M(IFNG) subset and reprograms M(IFNG) subset via ALDH2 (aldehyde dehydrogenase 2 family member) in ITP. Here, anti-ITGB3/CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to establish an active murine model of ITP. CMA activation diminished the pro-inflammatory and phagocytic activity of activated macrophages and ameliorated thrombocytopenia in ITP mice. MeRIP-sequencing identified PTEN (phosphatase and tensin homolog) as a crucial activator for LAMP2A, exhibiting decreased mA methylation and subsequent downregulation, which indicated a potential mechanism underlying CMA deficiency in activated macrophages. In conclusion, restoring CMA restrains the M(IFNG) subset and reprograms the M(IFNG) subset via ALDH2 to raise platelet counts in ITP. Targeting CMA in activated primary human macrophages presents a promising therapeutic strategy to rapidly and sustainably increase platelet counts and restore immune balance in ITP. ALDH2: aldehyde dehydrogenase 2 family member; ALKBH5: alkB homolog 5, RNA demethylase; CCL: C-C motif chemokine ligand; CMA: chaperone-mediated autophagy; CSF1/M-CSF: colony stimulating factor 1; CUT&Tag: Cleavage Under Targets and Tagmentation; CXCL: C-X-C motif chemokine ligand; FBS: fetal bovine serum; FCGR/FcγR: Fc gamma receptor; HLA-DR: major histocompatibility complex, class II, DR; IFNG/IFN-γ: interferon gamma; IGF2R: insulin like growth factor 2 receptor; IL: interleukin; ITP: immune thrombocytopenia; LAMP2A: lysosome associated membrane protein 2A; mA: N-methyladenosine; MeRIP-seq: methylated RNA immunoprecipitation sequencing; METTL3: methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit; MFI: mean fluorescence intensity; mRNA: messenger RNA; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NLRP3: NLR family pyrin domain containing 3; NOS2/iNOS: nitric oxide synthase 2; PBMCs: peripheral blood mononuclear cells; PTEN: phosphatase and tensin homolog; PYCARD: PYD and CARD domain containing; STAT: signal transducer and activator of transcription; Th1: T-helper 1; TNF: tumor necrosis factor; WTAP: WT1 associated protein. - Source: PubMed
Publication date: 2026/06/26
Xu YitongZhang PingWang LingjunWang HaoyiLi YubinMao JiahuiWang RuixueWang WanruGuo JinghanCao JunyingWang RutingHou MingHou Yu - Myelodysplastic neoplasms (MDS) feature hematopoietic deficits driven in part by transcript splicing abnormalities. Thus far, such disease-driving transcripts have been identified in association with specific splicing factor mutations. However, conserved aberrant splicing-derived transcripts that drive MDS independently of mutational status remain poorly studied despite representing global therapeutic targets. Here, we characterize an MDS-associated MBD1 isoform (MBD1-L) as a novel member of this class of transcripts. Rather than originating from a mutant splicing factor, the abnormal production of MBD1-L is driven by reduced WTAP expression in MDS. Overexpression of MBD1-L in healthy human HSPCs recapitulates archetypal MDS defects, including reduced terminal GLYA+ erythroid differentiation, suppressed cell cycling and impaired in vivo reconstitution capacity during increased hematopoietic demand in xenotransplantation assays. An integrated multiomics approach assessing DNA binding of MBD1 isoforms, and resulting changes in chromatin accessibility, histone mark deposition and transcriptional changes, revealed that these defects arise from an isoform-specific switching of MBD1's binding behavior. The MBD1-L isoform refocuses MBD1-L's heterochromatin-promoting activity from methylated to unmethylated CpGs and thus enacting broad downregulation of CpG-rich promoters as well as secondary epigenetic effects mediated by its downstream target BCOR. Remarkably, we also find that directly reversing abnormal MBD1 splicing across a broad range of primary human MDS samples using nanoparticle-encapsulated ASOs enhances in vitro erythroid differentiation, supporting the utility of RNA therapies for MDS treatment. Thus, our findings demonstrate MBD1-L to be a global, disease-driving splice variant across MDS, and illustrate the potential for RNA-based therapies in the broad treatment of MDS. - Source: PubMed
Publication date: 2026/06/18
Chen He Tian TonyJoshi PratikCathelin SeverineTazehkand Soheil JahangiriAdeel Saeer AXu JoshuaTsao EmilyMo YulinKealy DavidDowle AdamBalde ZaldyXuan MarryGowlett-Park DylanCzibere KatarinaMisura AlexandraBigun OlgaSasso RenatoLin AugustKundu NoorChadwick DianneUsta SilaKhazaee TinaChow SignyTsui HubertMinden Mark DHolding Andrew NBridge Katherine SZheng GangHope Kristin - Anaemia is a common global health problem affecting more than 500 million people worldwide. While N6-methyladenosine (mA) methylation is recognized as the most abundant internal (messenger ribonucleic acid (mRNA) modification that governs haematopoiesis, its specific function in erythropoiesis remains poorly understood. Here, we demonstrate that Wilms tumour 1-associating protein (WTAP), a core component of the mA methyltransferase complex, is highly expressed in erythroid progenitors and is expressed at low levels during differentiation. Depletion of WTAP compromises erythropoiesis both in vivo and in vitro, characterized by a profound reduction in erythroid progenitors and increased erythroblast apoptosis. Mechanistically, our findings demonstrate that WTAP-mediated mA modification is indispensable for maintaining normal erythropoiesis, orchestrating a broader regulatory network in which the signal transducer and activator of transcription 5 (STAT5) pathway acts as a critical, albeit not exclusive, downstream effector. - Source: PubMed
Publication date: 2026/06/19
Wu XiaYe WuLing YantaoWang XiaoJiaWang FangfangLiu XiaoyanYan TianyouGong Yuping - Preeclampsia (PE), a hypertensive disorder unique to pregnancy, is linked to impaired trophoblast function. DEAD-box helicase 39B (DDX39B) plays key roles in embryonic development. This study investigated its role in regulating trophoblast biology during PE progression. We conducted functional assays using CCK-8, clone formation, EdU, Transwell, Wound healing and TUNEL in the HTR-8/SVneo trophoblast cells. The interaction between Wilms tumor 1-associating protein (WTAP) and DDX39B was analyzed by Co-IP assay. RIP assay or RNA pull down were used to assess the association between the ELAV-like RNA-binding protein 1 (ELAVL1)/WTAP and L-lactate dehydrogenase A (LDHA) mRNA. Additionally, MeRIP assay was employed to evaluate m6A levels on LDHA transcripts. Overexpression of DDX39B promoted the proliferation and migration of trophoblast cells and suppressed cells apoptosis, while DDX39B knockdown had the opposite result. In addition, WTAP knockdown reversed the promoting effects of DDX39B overexpression on trophoblast proliferation and migration. Mechanistically, DDX39B promoted post-translational stabilization of WTAP by directly interacting with WTAP protein. WTAP enhanced the m6A methylation of LDHA mRNA by recruiting ELAVL1. As expected, LDHA knockdown abrogated the pro-proliferative and anti-apoptotic effects of WTAP overexpression on trophoblasts. Our findings established a novel DDX39B/WTAP/m6A/LDHA regulatory axis, wherein DDX39B acted as an RNA-binding protein to stabilize WTAP, enhancing LDHA expression and promoting trophoblast proliferation, migration, and survival. Dysregulation of this pathway might contribute to PE pathogenesis, offering new avenues for targeted therapies. - Source: PubMed
Publication date: 2026/06/19
Li ChengZhou WenjunShen YuqinZhang JingJiang YanqiongLi Ruiman