The function of Wtap in N6-adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells View Full Text


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Article Info

DATE

2022-07-25

AUTHORS

Taku Ito-Kureha, Cristina Leoni, Kayla Borland, Giulia Cantini, Marian Bataclan, Rebecca N. Metzger, Gregor Ammann, Anne B. Krug, Annalisa Marsico, Stefanie Kaiser, Stefan Canzar, Stefan Feske, Silvia Monticelli, Julian König, Vigo Heissmeyer

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. N6-methyladenosine (m6A) 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 m6A methyltransferase complex function and reveal its crucial role in TCR signaling in mouse T cells. 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 activity and diminished survival of T cells with conditional genetic inactivation of Wtap. These findings uncover how m6A modification impacts on TCR signal transduction and determines activation and survival of T cells. More... »

PAGES

1208-1221

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41590-022-01268-1

    DOI

    http://dx.doi.org/10.1038/s41590-022-01268-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1149723790

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35879451


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