| First Author | Yao Y | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 1333 |
| PubMed ID | 33637761 | Mgi Jnum | J:304853 |
| Mgi Id | MGI:6515123 | Doi | 10.1038/s41467-021-21594-6 |
| Citation | Yao Y, et al. (2021) METTL3-dependent m(6)A modification programs T follicular helper cell differentiation. Nat Commun 12(1):1333 |
| abstractText | T follicular helper (TFH) cells are specialized effector CD4(+) T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in TFH cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N(6)-methyladenosine (m(6)A) modification) in CD4(+) T cells impairs TFH differentiation and germinal center responses in a cell-intrinsic manner in mice. METTL3 is necessary for expression of important TFH signature genes, including Tcf7, Bcl6, Icos and Cxcr5 and these effects depend on intact methyltransferase activity. m(6)A-miCLIP-seq shows the 3' UTR of Tcf7 mRNA is subjected to METTL3-dependent m(6)A modification. Loss of METTL3 or mutation of the Tcf7 3' UTR m(6)A site results in accelerated decay of Tcf7 transcripts. Importantly, ectopic expression of TCF-1 (encoded by Tcf7) rectifies TFH defects owing to METTL3 deficiency. Our findings indicate that METTL3 stabilizes Tcf7 transcripts via m(6)A modification to ensure activation of a TFH transcriptional program, indicating a pivotal function of post-transcriptional regulation in promoting TFH cell differentiation. |
