The RNA m6A writer WTAP in diseases: structure, roles, and mechanisms

Abstract

N6-methyladenosine (m⁶A) is a widely investigated RNA modification in studies on the "epigenetic regulation" of mRNAs that is ubiquitously present in eukaryotes. Abnormal changes in m⁶A levels are closely related to the regulation of RNA metabolism, heat shock stress, tumor occurrence, and development. m⁶A modifications are catalyzed by the m⁶A 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 m⁶A 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 m⁶A modification. Then, we focus on WTAP, a component of the m⁶A methyltransferase complex, and introduce its structure, localization, and physiological functions. Finally, we describe its roles and mechanisms in cancer.