Pre-mRNA-splicing regulator WTAP (WTAP)

Pre-mRNA-splicing regulator WTAP (WTAP) is a ubiquitously expressed nuclear protein encoded by the WTAP gene, functioning primarily as an RNA-binding protein that regulates alternative splicing of pre-mRNA and serves as a core regulatory subunit of the N6-methyladenosine (m6A) methyltransferase ("writer") complex (with METTL3 and METTL14), guiding methyltransferase localization to target RNAs. WTAP modulates key cellular processes including mRNA splicing, mRNA stability, and cell cycle progression, is necessary for embryogenesis, and has roles in the regulation of cell proliferation, differentiation, and apoptosis. Dysregulation or overexpression of WTAP has been linked to various cancers both as a driver of proliferation and as a mediator of chemoresistance, highlighting its potential as a therapeutic target and biomarker in oncology. Direct pharmacological inhibitors or agonists of WTAP have not been established, but the pathway is considered an attractive emerging target for cancer therapy and for understanding post-transcriptional gene regulation.

Other names

Wilms tumor 1-associating proteinWilms tumor 1 associated proteinPre-mRNA-splicing regulator WTAPKIAA0105hFL(2)DMGC3925Mum2Female-lethal(2)D homologPNAS-132

Not well-established for direct WTAP-targeting drugs. Indirectly, WTAP’s activity in mRNA stabilization and m6A modification can regulate expression of drug resistance genes such as MRP1 and P-gp, influencing chemoresistance.