The RNA m6A writer METTL14 in cancers: Roles, structures, and applications

N-6-methyladenosine (m(6)A) is the most abundant and diverse epigenetic modification of mRNAs in eukaryotes, and it regulates biological metabolism, cell differentiation and cycles, and responses to heat shock stress, cancers and other diseases. RNA methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14) and other proteins possessing methyltransferase (MTase) capability including Wilms tumor 1-associated protein (WTAP), RNA-binding motif protein 15(RBM15), KIAA1429 and zinc finger CCCH-type containing 13 (ZC3H13) constitute the m(6)A writer complex. Although METTL3 is the catalytic subunit, its activity is strongly dependent on METTL14, which is crucial in maintaining complex integrity and recognizing special RNA substrates. Currently, the roles of m(6)A modification in cancers are being extensively reviewed. The critical functions of METTL14 in the occurrence and development of a variety of cancers as well as the potential targeting of METTL14 as a cancer treatment have not yet been highlighted. Therefore, in this review, we summarize the m(6)A modification and focus on the structure and functions of METTL14 as well as its roles in oncogenesis, metastasis progression, treatment and prognosis in cancer.

Automated summary

m(6)A modification is the most abundant and diverse epigenetic modification of mRNAs in eukaryotes, regulating biological metabolism, cell differentiation, and responses to diseases. METTL3 and METTL14 are key components of the m(6)A writer complex, with METTL14 crucial for complex integrity and recognizing special RNA substrates, and its roles in cancer are currently being extensively reviewed.