N6-methyladenosine RNA modification: an emerging molecule in type 2 diabetes metabolism

Abstract

Type 2 diabetes (T2D) is a metabolic disease with an increasing rate of incidence worldwide. Despite the considerable progress in the prevention and intervention, T2D and its complications cannot be reversed easily after diagnosis, thereby necessitating an in-depth investigation of the pathophysiology. In recent years, the role of epigenetics has been increasingly demonstrated in the disease, of which N6-methyladenosine (m6A) is one of the most common post-transcriptional modifications. Interestingly, patients with T2D show a low m6A abundance. Thus, a comprehensive analysis and understanding of this phenomenon would improve our understanding of the pathophysiology, as well as the search for new biomarkers and therapeutic approaches for T2D. In this review, we systematically introduced the metabolic roles of m6A modification in organs, the metabolic signaling pathways involved, and the effects of clinical drugs on T2D.

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

“…Moreover, Vir-like m 6 A methyltransferase-associated (VIRMA, also known as KIAA1429), RNA-binding motif protein 15 (RBM15) and its paralog RBM15B have been recognized as additional components of the m 6 A writer complex, expanding the regulatory landscape (19). Currently, novel methyltransferases, such as METTL4, METTL5, METTL16, and zinc finger CCCH domain-containing protein 13 (ZC3H13), has been identified as modifiers to affect RNA metabolism in diabetes and its complications (20)(21)(22), showcasing their adaptability to diverse RNA substrates.…”

Comprehensive analysis of m6A modification in lipopolysaccharide-induced acute lung injury in mice

“…Readers recognize methylated m6A sites on RNA and affect RNA fate, which include YTH domain containing proteins 1/2 (YTHDC1/2), YTH-family proteins 1–3 (YTHDF1-3) and insulin-like growth factor 2 mRNA binding proteins 1–3 (IGF2BP1-3)(Huang et al 2021 ; Tian et al 2021 ; Wang et al 2022b ). Similar to other RNA post-transcriptional modification, m6A modification regulates key biological processes, including splicing, nuclear export, translation, mRNA stabilization, and mRNA degradation (Garbo et al 2021 ; Valadon et al 2021 ; Zhang et al 2023 ). And m6A modification is considered to be closely correlated with a variety of physiological and pathological processes (Bu et al 2023 ; Li et al 2021 ; Wang et al, 2022c ; Zhang et al, 2022d ).…”