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| Status |
Public on Jan 16, 2024 |
| Title |
The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Post-transcriptional control by RNA-binding proteins (RBPs) is an essential layer of gene regulation in lymphocytes. Here, we show how members of the R3hdm RBP family regulate gene expression and promote the development of thymocytes. R3hdm paralogs with an intact R3H/SUZ domain bound mRNAs of other RBPs including Roquin-1, Roquin-2 and Nufip2, and augmented their expression. Arpp21 (R3hdm3) expression was restricted to thymocyte stages when Rag proteins recombine gene segments of the TCR variable region. Crosslinking and immunoprecipitation of Arpp21 in thymocytes revealed prominent binding to the Rag1 mRNA, and Arpp21 increased Rag1 3'-UTR reporter expression. Consequently, Arpp21–deficient mice showed decreased Rag1 expression in thymocytes, delayed TCR rearrangement, reduced frequencies of cells with TCR expression and a partial block of thymocyte development. The Arpp21 protein was regulated by Ca2+–signals that induced phosphorylation, polyubiquitination and proteasomal degradation. These findings involve general redundant functions of R3hdm RBP family proteins and show how stage-specific upregulation of Arpp21 in thymocytes promotes Rag1 expression preceding recombination while productive TCR rearrangement ceases this function.
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| Overall design |
Examination of transcriptome in WT or Arpp12 KO thymocytes. The Arpp21-CLIP experiment were performed on polyA+ RNA from thymocytes with 4 biological replicates.
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| Web link |
http://10.1038/s41467-024-46371-z
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| |
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| Contributor(s) |
Xu M, Straub T, Heissmeyer V |
| Citation(s) |
38467629 |
| |
| Submission date |
Mar 16, 2022 |
| Last update date |
Apr 16, 2024 |
| Contact name |
Taku Kureha |
| E-mail(s) |
Taku.Kureha@med.uni-muenchen.de
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| Phone |
+49-(0)89-2180-71211
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| Organization name |
Ludwig-Maximilians-Universität
|
| Department |
Institute for Immunology
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| Lab |
Molecular Immune Regulation
|
| 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 (11)
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| This SubSeries is part of SuperSeries: |
| GSE198798 |
The RNA-binding protein Arpp21 interacts with and promotes Rag1 target mRNA expression to enable TCR rearrangement |
|
| Relations |
| BioProject |
PRJNA816898 |
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