METTL3-m⁶A-Rubicon axis inhibits autophagy in nonalcoholic fatty liver disease.

ABSTRACT: N6-methyladenosine (m⁶A) mRNA modification plays critical roles in various biological events and is involved in multiple complex diseases. However, the role of m⁶A modification in autophagy in nonalcoholic fatty liver disease (NAFLD) remains largely unknown. Here, we report that m⁶A modification was increased in livers of NAFLD mouse models and in free fatty acid (FFA)-treated hepatocytes, and the abnormal m⁶A modification was attributed to the upregulation of methyltransferase like 3 (METTL3) induced by lipotoxicity. Knockdown of METTL3 promoted hepatic autophagic flux and clearance of lipid droplets (LDs), while overexpression of METTL3 inhibited these processes. Mechanistically, METTL3 directly bound to Rubicon mRNA and mediated the m⁶

SUBMITTER: Peng Z 

PROVIDER: S-EPMC8821937 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature