METTL3-dependent m⁶A modification programs T follicular helper cell differentiation.

ABSTRACT: T follicular helper (T_FH) cells are specialized effector CD4⁺ T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in T_FH cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N⁶-methyladenosine (m⁶A) modification) in CD4⁺ T cells impairs T_FH differentiation and germinal center responses in a cell-intrinsic manner in mice. METTL3 is necessary for expression of important T_FH signature genes, including Tcf7, Bcl6, Icos and Cxcr5 and these effects depend on intact methyltransferase activity. m⁶A-miCLIP-seq shows the 3' UTR of Tcf7 mRNA is subjected to METTL3-dependent m⁶A modification. Loss of METTL3

SUBMITTER: Yao Y 

PROVIDER: S-EPMC7910450 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature