M⁶A mRNA methylation regulates testosterone synthesis through modulating autophagy in Leydig cells.

ABSTRACT: Macroautophagy/autophagy is indispensable for testosterone synthesis in Leydig cells (LCs), and here we report a negative association between m⁶A modification and autophagy in LCs during testosterone synthesis. A gradual decrease of METTL14 (methyltransferase like 14) and an increase of ALKBH5 (alkB homolog 5, RNA demethylase) were observed in LCs during their differentiation from stem LCs to adult LCs. These events led to reduced mRNA methylation levels of N⁶-methyladenosine (m⁶A) and enhanced autophagy in LCs. Similar regulation of METTL14, ALKBH5, and m⁶A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Mechanistically, m⁶A modification promoted translation of PPM1A (protein phosphatase 1A, magnesium

SUBMITTER: Chen Y 

PROVIDER: S-EPMC8007139 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature