Wilms tumor 1-associated protein (WTAP) (WTAP)

Wilms tumor 1-associated protein (WTAP) mRNA is a significant therapeutic target in the field of epitranscriptomics, as it encodes the essential regulatory subunit of the N6-methyladenosine (m6A) methyltransferase complex (UniProt Q15007). The WTAP protein is required for the recruitment of the catalytic components METTL3 and METTL14 to nuclear speckles, where they perform m6A methylation on target transcripts (PubMed: 24403073). This modification is a key regulator of RNA stability, splicing, and translation, influencing critical cellular processes such as the cell cycle and differentiation (PubMed: 31105119). In various malignancies, including acute myeloid leukemia and hepatocellular carcinoma, WTAP mRNA is frequently overexpressed, leading to increased m6A levels that promote oncogenic signaling (PubMed: 33414416). Therapeutic strategies targeting WTAP mRNA primarily utilize RNA interference (RNAi), such as siRNAs or shRNAs, to induce transcript degradation and subsequent depletion of the WTAP protein (PubMed: 31105119). Such interventions have been shown to inhibit tumor growth and induce apoptosis in preclinical models by disrupting the m6A writer complex. However, the essential role of WTAP in normal development and its association with embryonic lethality pose substantial safety concerns for the clinical translation of WTAP-targeted therapies (PubMed: 24403073).

Other names

WT1-associated proteinFemale-lethal(2)D homologhFL(2)DMum2

RNA interference (RNAi) targeting WTAP mRNA to induce its degradation, thereby preventing the translation of WTAP protein and disrupting the assembly of the m6A methyltransferase complex (PubMed: 31105119).