The RNA m(6)A writer WTAP in diseases: structure, roles, and mechanisms

N6-methyladenosine (m(6)A) is a widely investigated RNA modification in studies on the “epigenetic regulation” of mRNAs that is ubiquitously present in eukaryotes. Abnormal changes in m(6)A levels are closely related to the regulation of RNA metabolism, heat shock stress, tumor occurrence, and development. m(6)A modifications are catalyzed by the m(6)A writer complex, which contains RNA methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), Wilms tumor 1-associated protein (WTAP), and other proteins with methyltransferase (MTase) capability, such as RNA-binding motif protein 15 (RBM15), KIAA1429 and zinc finger CCCH-type containing 13 (ZC3H13). Although METTL3 is the main catalytic subunit, WTAP is a regulatory subunit whose function is to recruit the m(6)A methyltransferase complex to the target mRNA. Specifically, WTAP is required for the accumulation of METTL3 and METTL14 in nuclear speckles. In this paper, we briefly introduce the molecular mechanism of m(6)A modification. Then, we focus on WTAP, a component of the m(6)A methyltransferase complex, and introduce its structure, localization, and physiological functions. Finally, we describe its roles and mechanisms in cancer.