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| Status |
Public on Jun 03, 2022 |
| Title |
The function of Wtap in N6-adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells [m6A-CLIP] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Examination of transcriptome in WT or Wtap KO CD4+ T cells. m6A-CLIP or YTHDF2-iCLIP experiments were performed on polyA+ RNA from mouse CD4+ cells with 3 or 2 biological replicates, respectively.
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| Contributor(s) |
Ito-Kureha T, Heissmeyer V |
| Citation(s) |
35879451 |
| |
| Submission date |
Nov 15, 2021 |
| Last update date |
Nov 04, 2022 |
| Contact name |
Taku Kureha |
| E-mail(s) |
Taku.Kureha@med.uni-muenchen.de
|
| Phone |
+49-(0)89-2180-71211
|
| Organization name |
Ludwig-Maximilians-Universität
|
| Department |
Institute for Immunology
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| Lab |
Molecular Immune Regulation
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| Street address |
Grosshaderner Str. 9
|
| City |
Planegg-Martinsried |
| ZIP/Postal code |
82152 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE188854 |
The function of Wtap in N6-adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells |
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| Relations |
| BioProject |
PRJNA780524 |
| SRA |
SRP346159 |
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