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Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation

The (m7)G cap is ubiquitous on RNAPII-transcribed RNA and has fundamental roles in eukaryotic gene expression, however its in vivo role in mammals has remained unknown. Here, we identified the (m7)G cap methyltransferase, RNMT, as a key mediator of T cell activation, which specifically regulates rib...

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Autores principales: Galloway, Alison, Kaskar, Aneesa, Ditsova, Dimitrinka, Atrih, Abdelmadjid, Yoshikawa, Harunori, Gomez-Moreira, Carolina, Suska, Olga, Warminski, Marcin, Grzela, Renata, Lamond, Angus I, Darzynkiewicz, Edward, Jemielity, Jacek, Cowling, Victoria H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266598/
https://www.ncbi.nlm.nih.gov/pubmed/34125914
http://dx.doi.org/10.1093/nar/gkab465
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author Galloway, Alison
Kaskar, Aneesa
Ditsova, Dimitrinka
Atrih, Abdelmadjid
Yoshikawa, Harunori
Gomez-Moreira, Carolina
Suska, Olga
Warminski, Marcin
Grzela, Renata
Lamond, Angus I
Darzynkiewicz, Edward
Jemielity, Jacek
Cowling, Victoria H
author_facet Galloway, Alison
Kaskar, Aneesa
Ditsova, Dimitrinka
Atrih, Abdelmadjid
Yoshikawa, Harunori
Gomez-Moreira, Carolina
Suska, Olga
Warminski, Marcin
Grzela, Renata
Lamond, Angus I
Darzynkiewicz, Edward
Jemielity, Jacek
Cowling, Victoria H
author_sort Galloway, Alison
collection PubMed
description The (m7)G cap is ubiquitous on RNAPII-transcribed RNA and has fundamental roles in eukaryotic gene expression, however its in vivo role in mammals has remained unknown. Here, we identified the (m7)G cap methyltransferase, RNMT, as a key mediator of T cell activation, which specifically regulates ribosome production. During T cell activation, induction of mRNA expression and ribosome biogenesis drives metabolic reprogramming, rapid proliferation and differentiation generating effector populations. We report that RNMT is induced by T cell receptor (TCR) stimulation and co-ordinates the mRNA, snoRNA and rRNA production required for ribosome biogenesis. Using transcriptomic and proteomic analyses, we demonstrate that RNMT selectively regulates the expression of terminal polypyrimidine tract (TOP) mRNAs, targets of the (m7)G-cap binding protein LARP1. The expression of LARP1 targets and snoRNAs involved in ribosome biogenesis is selectively compromised in Rnmt cKO CD4 T cells resulting in decreased ribosome synthesis, reduced translation rates and proliferation failure. By enhancing ribosome abundance, upregulation of RNMT co-ordinates mRNA capping and processing with increased translational capacity during T cell activation.
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spelling pubmed-82665982021-07-09 Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation Galloway, Alison Kaskar, Aneesa Ditsova, Dimitrinka Atrih, Abdelmadjid Yoshikawa, Harunori Gomez-Moreira, Carolina Suska, Olga Warminski, Marcin Grzela, Renata Lamond, Angus I Darzynkiewicz, Edward Jemielity, Jacek Cowling, Victoria H Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The (m7)G cap is ubiquitous on RNAPII-transcribed RNA and has fundamental roles in eukaryotic gene expression, however its in vivo role in mammals has remained unknown. Here, we identified the (m7)G cap methyltransferase, RNMT, as a key mediator of T cell activation, which specifically regulates ribosome production. During T cell activation, induction of mRNA expression and ribosome biogenesis drives metabolic reprogramming, rapid proliferation and differentiation generating effector populations. We report that RNMT is induced by T cell receptor (TCR) stimulation and co-ordinates the mRNA, snoRNA and rRNA production required for ribosome biogenesis. Using transcriptomic and proteomic analyses, we demonstrate that RNMT selectively regulates the expression of terminal polypyrimidine tract (TOP) mRNAs, targets of the (m7)G-cap binding protein LARP1. The expression of LARP1 targets and snoRNAs involved in ribosome biogenesis is selectively compromised in Rnmt cKO CD4 T cells resulting in decreased ribosome synthesis, reduced translation rates and proliferation failure. By enhancing ribosome abundance, upregulation of RNMT co-ordinates mRNA capping and processing with increased translational capacity during T cell activation. Oxford University Press 2021-06-14 /pmc/articles/PMC8266598/ /pubmed/34125914 http://dx.doi.org/10.1093/nar/gkab465 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Galloway, Alison
Kaskar, Aneesa
Ditsova, Dimitrinka
Atrih, Abdelmadjid
Yoshikawa, Harunori
Gomez-Moreira, Carolina
Suska, Olga
Warminski, Marcin
Grzela, Renata
Lamond, Angus I
Darzynkiewicz, Edward
Jemielity, Jacek
Cowling, Victoria H
Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation
title Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation
title_full Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation
title_fullStr Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation
title_full_unstemmed Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation
title_short Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation
title_sort upregulation of rna cap methyltransferase rnmt drives ribosome biogenesis during t cell activation
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266598/
https://www.ncbi.nlm.nih.gov/pubmed/34125914
http://dx.doi.org/10.1093/nar/gkab465
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