Aberrant METTL1-mediated tRNA m⁷G modification alters B-cell responses in systemic autoimmunity in humans and mice.

ABSTRACT: Upon activation, naive B cells exit their quiescent state and enter germinal center (GC) responses, a transition accompanied by increased protein synthesis. How protein translation efficiency is adequately adjusted to meet the increased demand requires further investigation. Here, we identify the methyltransferase METTL1 as a translational checkpoint during GC responses. Conditional knockout of Mettl1 in mouse B cells blocks GC entry and impairs GC formation, whereas conditional knock-in of Mettl1 promotes GC responses. Mechanistically, METTL1 catalyzes m⁷G modification in a specific subset of tRNAs to preferentially translate BCR signaling-related proteins, ensuring mitochondrial electron transporter chain activity and sufficient bioenergetics in B cells. Pathologically, METTL1

SUBMITTER: Wang S 

PROVIDER: S-EPMC11621805 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature