Back to Search
Start Over
The function of Wtap in N 6 -adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells.
- Source :
-
Nature immunology [Nat Immunol] 2022 Aug; Vol. 23 (8), pp. 1208-1221. Date of Electronic Publication: 2022 Jul 25. - Publication Year :
- 2022
-
Abstract
- T cell antigen-receptor (TCR) signaling controls the development, activation and survival of T cells by involving several layers and numerous mechanisms of gene regulation. N <superscript>6</superscript> -methyladenosine (m <superscript>6</superscript> A) is the most prevalent messenger RNA modification affecting splicing, translation and stability of transcripts. In the present study, we describe the Wtap protein as essential for m <superscript>6</superscript> A methyltransferase complex function and reveal its crucial role in TCR signaling in mouse T cells. Wtap and m <superscript>6</superscript> A methyltransferase functions were required for the differentiation of thymocytes, control of activation-induced death of peripheral T cells and prevention of colitis by enabling gut RORγt <superscript>+</superscript> regulatory T cell function. Transcriptome and epitranscriptomic analyses reveal that m <superscript>6</superscript> A modification destabilizes Orai1 and Ripk1 mRNAs. Lack of post-transcriptional repression of the encoded proteins correlated with increased store-operated calcium entry activity and diminished survival of T cells with conditional genetic inactivation of Wtap. These findings uncover how m <superscript>6</superscript> A modification impacts on TCR signal transduction and determines activation and survival of T cells.<br /> (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 23
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 35879451
- Full Text :
- https://doi.org/10.1038/s41590-022-01268-1