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Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410761/
https://www.ncbi.nlm.nih.gov/pubmed/34471108
http://dx.doi.org/10.1038/s41467-021-25345-5
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author 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
author_facet 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
author_sort Hoefig, Kai P.
collection PubMed
description 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.
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spelling pubmed-84107612021-09-22 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 Nat Commun Article 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. Nature Publishing Group UK 2021-09-01 /pmc/articles/PMC8410761/ /pubmed/34471108 http://dx.doi.org/10.1038/s41467-021-25345-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
title Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
title_full Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
title_fullStr Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
title_full_unstemmed Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
title_short Defining the RBPome of primary T helper cells to elucidate higher-order Roquin-mediated mRNA regulation
title_sort defining the rbpome of primary t helper cells to elucidate higher-order roquin-mediated mrna regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410761/
https://www.ncbi.nlm.nih.gov/pubmed/34471108
http://dx.doi.org/10.1038/s41467-021-25345-5
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