METTL14-Induced M⁶A Methylation Increases G6pc Biosynthesis, Hepatic Glucose Production and Metabolic Disorders in Obesity.

ABSTRACT: METTL14 dimerizes with METTL3 to install N6-methyladenosine (m⁶A) on mRNA (m⁶A writers). Subsequently, m⁶A readers bind to m⁶A-marked RNA to influence its metabolism. RNA m⁶A emerges to critically regulate multiple intracellular processes; however, there is a gap in our understanding of m⁶A in liver metabolism. Glucose-6-phosphatase catalytic subunit (G6pc) mediates hepatic glucose production (HGP) and serves as the gatekeeper for glycogenolysis and gluconeogenesis; however, G6pc regulation is not fully understood. Here, METTL14 is identified as a posttranscriptional regulator of G6pc. Liver METTL14, METTL3, and m⁶A-methylated G6pc mRNA are upregulated in mice with diet-induced obesity. Deletion of Mettl14 decreas

SUBMITTER: Zheng Q 

PROVIDER: S-EPMC12165098 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature