Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
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Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation. / Hoefig, Kai P; Reim, Alexander; Gallus, Christian; Wong, Elaine H; Behrens, Gesine; Conrad, Christine; Xu, Meng; Kifinger, Lisa; Ito-Kureha, Taku; Defourny, Kyra A Y; Geerlof, Arie; Mautner, Josef; Hauck, Stefanie M; Baumjohann, Dirk; Feederle, Regina; Mann, Matthias; Wierer, Michael; Glasmacher, Elke; Heissmeyer, Vigo.
In: Nature Communications, Vol. 12, No. 1, 01.09.2021, p. 5208.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
AU - Hoefig, Kai P
AU - Reim, Alexander
AU - Gallus, Christian
AU - Wong, Elaine H
AU - Behrens, Gesine
AU - Conrad, Christine
AU - Xu, Meng
AU - Kifinger, Lisa
AU - Ito-Kureha, Taku
AU - Defourny, Kyra A Y
AU - Geerlof, Arie
AU - Mautner, Josef
AU - Hauck, Stefanie M
AU - Baumjohann, Dirk
AU - Feederle, Regina
AU - Mann, Matthias
AU - Wierer, Michael
AU - Glasmacher, Elke
AU - Heissmeyer, Vigo
N1 - © 2021. The Author(s).
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
KW - Animals
KW - DNA-Binding Proteins
KW - Gene Expression Regulation
KW - HEK293 Cells
KW - Humans
KW - Inducible T-Cell Co-Stimulator Protein/genetics
KW - Mice
KW - Proto-Oncogene Proteins c-vav
KW - RNA, Messenger/metabolism
KW - RNA-Binding Proteins/genetics
KW - STAT1 Transcription Factor
KW - STAT4 Transcription Factor
KW - Signal Transduction
KW - T-Lymphocytes, Helper-Inducer/metabolism
KW - Trans-Activators/metabolism
KW - Ubiquitin-Protein Ligases/genetics
U2 - 10.1038/s41467-021-25345-5
DO - 10.1038/s41467-021-25345-5
M3 - Journal article
C2 - 34471108
VL - 12
SP - 5208
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
ER -
ID: 303116308