m6 A mRNA methylation: Biological features, mechanisms, and therapeutic potentials in type 2 diabetes mellitus

Obes Rev. 2023 Dec;24(12):e13639. doi: 10.1111/obr.13639. Epub 2023 Sep 21.

Abstract

As the most common internal post-transcriptional RNA modification in eukaryotic cells, N6-methyladenosine (m6 A) performs a dynamic and reversible role in a variety of biological processes mediated by methyltransferases (writers), demethylases (erasers), and m6 A binding proteins (readers). M6 A methylation enables transcriptome conversion in different signals that regulate various physiological activities and organ development. Over the past few years, emerging studies have identified that mRNA m6 A regulators defect in β-cell leads to abnormal regulation of the target mRNAs, thereby resulting in β-cell dysfunction and loss of β-cell identity and mass, which are strongly associated with type 2 diabetes mellitus (T2DM) pathogenesis. Also, mRNA m6 A modification has been implicated with insulin resistance in muscles, fat, and liver cells/tissues. In this review, we elaborate on the biological features of m6 A methylation; provide a comprehensive overview of the underlying mechanisms that how it controls β-cell function, identity, and mass as well as insulin resistance; highlight its connections to glucose metabolism and lipid metabolism linking to T2DM; and further discuss its role in diabetes complications and its therapeutic potentials for T2DM diagnosis and treatment.

Keywords: m6A methylation; mechanisms; therapeutic potentials; type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2* / genetics
  • Humans
  • Insulin Resistance* / genetics
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Methyltransferases
  • RNA, Messenger