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

Abstract

SummaryAs the most common internal post‐transcriptional RNA modification in eukaryotic cells, N6‐methyladenosine (m6A) performs a dynamic and reversible role in a variety of biological processes mediated by methyltransferases (writers), demethylases (erasers), and m6A binding proteins (readers). M6A 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 m6A 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 m6A modification has been implicated with insulin resistance in muscles, fat, and liver cells/tissues. In this review, we elaborate on the biological features of m6A 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.

The m6A-ncRNAs axis in diabetes complications: novel mechanism and therapeutic potential

“…Conclusively, the dynamic interplay among m 6 A writers, erasers, and readers regulates fundamental cellular processes, including RNA processing, stability, and translation. In diabetes and its complications, the dysregulation of m 6 A modifiers is instrumental in determining the cellular RNA methylation landscape, ultimately affecting gene expression and biological processes, such as pancreatic β-cell dysfunction, insulin resistance, and abnormal lipid metabolism ( 5 , 22 , 38 ). As vital gene regulators, ncRNAs have also been implicated in the occurrence and progression of metabolic diseases.…”

Identifying Potent Fat Mass and Obesity-Associated Protein Inhibitors Using Deep Learning-Based Hybrid Procedures

“…The FTO gene, which is responsible for encoding a dioxygenase enzyme belonging to the AlkB family and dependent on 2-oxoglutarate (2-OG) Fe(II), is situated on chromosome 16q12.2 [24]. The FTO gene exhibits significant expression in adipose tissues and skeletal muscles within human anatomical structures [25]. Notably, the highest expression level is observed in the hypothalamus, specifically in the arcuate nucleus, which governs energy balance [26].…”