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

Qibo HuangJie MoZhibin LiaoXiao-Ping ChenBixiang Zhang
Published in: Cell death & disease (2022)
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.
Keyphrases
  • heat shock
  • nucleic acid
  • binding protein
  • transcription factor
  • papillary thyroid
  • heat stress
  • oxidative stress
  • young adults
  • dna binding
  • single molecule
  • crystal structure