m⁶A mRNA methylation: Biological features, mechanisms, and therapeutic potentials in type 2 diabetes mellitus

As the most common internal post-transcriptional RNA modification in eukaryotic cells, N6-methyladenosine (m(6)A) performs a dynamic and reversible role in a variety of biological processes mediated by methyltransferases (writers), demethylases (erasers), and m(6)A binding proteins (readers). M(6)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 m(6)A regulators defect in beta-cell leads to abnormal regulation of the target mRNAs, thereby resulting in beta-cell dysfunction and loss of beta-cell identity and mass, which are strongly associated with type 2 diabetes mellitus (T2DM) pathogenesis. Also, mRNA m(6)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 m(6)A methylation; provide a comprehensive overview of the underlying mechanisms that how it controls beta-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.