Defining the RBPome of T helper cells to study higher order post-transcriptional gene 1 regulation

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):

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