Defining the RBPome of T helper cells to study higher order post-transcriptional gene 1 regulation
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ABSTRACT: Post-transcriptional gene regulation in T cells is dynamic and complex as targeted transcripts respond to various factors. This becomes evident for the Icos mRNA encoding an essential costimulatory receptorthatexhibits coordinate regulation by several RNA-binding proteins (RBPs), including Roquin-1 and Roquin-2. Utilizing global RNA interactome capture (RNA-IC) and orthogonal organic phase separation (OOPS) we identify a core RBPome of 798 mouse and 801 human T cell proteins. The RBPome also contained Stat1, Stat4 and Vav1 proteins suggesting unexpected functions for these transcription factors and signal transducers. Based on proximity to Roquin-1, we selected ~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 unraveled Roquin-1/2-dependent and target-specific coregulation of Icos byCelf1 and Igf2bp3. These findings define the cellular RBPome as post-transcriptional context that predetermines the extent of target regulation by individual trans-acting factors.
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Embryonic Fibroblast, T Cell
SUBMITTER: Juliane Merl-Pham
LAB HEAD: Vigo Heissmeyer
PROVIDER: PXD026716 | Pride | 2021-06-28
REPOSITORIES: Pride
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