N6-adenosine methylation of mRNAs requires Wtap expression and controls T cell receptor signaling and survival
Informazioni aggiuntive
Autori
Ito-Kureha T.,
Leoni C.,
Borland K.,
Bataclan M.,
Metzger R. N.,
Ammann G.,
Krug A. B.,
Marsico A.,
Kellner S.,
Canzar S.,
Feske S.,
Monticelli S.,
König J.,
Heissmeyer V.
Tipo
Preprint
Anno
2021
Lingua
Inglese
Sommario
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. N6-methyladenosine (m6A) is the most prevalent mRNA modification affecting splicing, translation and stability of transcripts. Here, we describe the Wtap protein as essential for m6A methyltransferase complex function and reveal its crucial role in TCR signaling. Wtap and m6A 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+ regulatory T cell function. Transcriptome and epitranscriptomic analyses reveal that m6A modification destabilizes Orai1 and Ripk1 mRNAs. Lack of post-transcriptional repression of the encoded proteins correlated with increased store-operated calcium entry (SOCE) activity and diminished survival of T cells. These findings uncover how m6A modification impacts on TCR signal transduction and determines activation and survival of T cells.
Parole chiave
T cell antigen receptor, m6A, Wtap protein
Periodico
Nature Immunology
Diffusione
Licenza
CC BY
Visibilità
Pubblico
Status open access
Green
