Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
Research output: Contribution to journal › Journal article › Research › peer-review
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 costimulatory 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 ~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.
| Original language | English |
|---|---|
| Journal | Nature Communications |
| Volume | 12 |
| Issue number | 1 |
| Pages (from-to) | 5208 |
| ISSN | 2041-1723 |
| DOIs | |
| Publication status | Published - 1 Sep 2021 |
| Externally published | Yes |
Bibliographical note
© 2021. The Author(s).
- Animals, DNA-Binding Proteins, Gene Expression Regulation, HEK293 Cells, Humans, Inducible T-Cell Co-Stimulator Protein/genetics, Mice, Proto-Oncogene Proteins c-vav, RNA, Messenger/metabolism, RNA-Binding Proteins/genetics, STAT1 Transcription Factor, STAT4 Transcription Factor, Signal Transduction, T-Lymphocytes, Helper-Inducer/metabolism, Trans-Activators/metabolism, Ubiquitin-Protein Ligases/genetics
Research areas
ID: 303116308