m⁶ A 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 (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.