Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25345-5
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Funding
- German Research Foundation [SPP-1935, SFB-1054]
- Wilhelm Sander foundation
- Fritz Thyssen foundation
- Else Kroner-Fresenius foundation
- Deutsche Krebshilfe foundation
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [BA 5132/1-1, BA 5132/1 2, 252623821, 210592381]
- Germany's Excellence Strategy EXC2151 [390873048]
- [HE3359/7-1]
- [HE3359/8-1]
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Post-transcriptional gene regulation in T cells is a dynamic and complex process, involving multiple RNA-binding proteins and unexpected functions for certain transcription factors and signal transducers. By studying the regulation of Roquin-1 and Roquin-2, it was found that multiple RBPs contribute to the coregulation of mRNA targets by individual trans-acting factors.
Post-transcriptional gene regulation in T cells is dynamic and complex as targeted transcripts respond to various factors. This is evident for the Icos mRNA encoding an essential costi-mulatory receptor that is regulated by several RNA-binding proteins (RBP), including Roquin-1 and Roquin-2. Here, we identify a core RBPome of 798 mouse and 801 human T cell proteins by utilizing global RNA interactome capture (RNA-IC) and orthogonal organic phase separation (OOPS). The RBPome includes Stat1, Stat4 and Vav1 proteins suggesting unexpected functions for these transcription factors and signal transducers. Based on proximity to Roquin-1, we select similar to 50 RBPs for testing coregulation of Roquin-1/2 targets by induced expression in wild-type or Roquin-1/2-deficient T cells. Besides Roquin-independent contributions from Rbms1 and Cpeb4 we also show Roquin-1/2-dependent and target-specific coregulation of Icos by Celf1 and Igf2bp3. Connecting the cellular RBPome in a post-transcriptional context, we find contributions from multiple RBPs to the prototypic regulation of mRNA targets by individual trans-acting factors.
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