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PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation
Protein arginine methyltransferases (PRMTs) are a family of enzymes that modify proteins by methylating the guanidino nitrogen atoms of arginine residues to regulate cellular processes such as chromatin remodeling, pre-mRNA splicing, and signal transduction. PRMT7 is the single type III PRMT solely...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589776/ https://www.ncbi.nlm.nih.gov/pubmed/30699057 http://dx.doi.org/10.1091/mbc.E18-05-0330 |
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author | Haghandish, Nasim Baldwin, R. Mitchell Morettin, Alan Dawit, Haben Tesfu Adhikary, Hemanta Masson, Jean-Yves Mazroui, Rachid Trinkle-Mulcahy, Laura Côté, Jocelyn |
author_facet | Haghandish, Nasim Baldwin, R. Mitchell Morettin, Alan Dawit, Haben Tesfu Adhikary, Hemanta Masson, Jean-Yves Mazroui, Rachid Trinkle-Mulcahy, Laura Côté, Jocelyn |
author_sort | Haghandish, Nasim |
collection | PubMed |
description | Protein arginine methyltransferases (PRMTs) are a family of enzymes that modify proteins by methylating the guanidino nitrogen atoms of arginine residues to regulate cellular processes such as chromatin remodeling, pre-mRNA splicing, and signal transduction. PRMT7 is the single type III PRMT solely capable of arginine monomethylation. To date, other than histone proteins, there are very few identified substrates of PRMT7. We therefore performed quantitative mass spectrometry experiments to identify PRMT7’s interactome and potential substrates to better characterize the enzyme’s biological function(s) in cells. These experiments revealed that PRMT7 interacts with and can methylate eukaryotic translation initiation factor 2 alpha (eIF2α), in vitro and in breast cancer cells. Furthermore, we uncovered a potential regulatory interplay between eIF2α arginine methylation by PRMT7 and stress-induced phosphorylation status of eIF2α at serine 51. Finally, we demonstrated that PRMT7 is required for eIF2α-dependent stress granule formation in the face of various cellular stresses. Altogether, our findings implicate PRMT7 as a novel mediator of eIF2α-dependent cellular stress response pathways. |
format | Online Article Text |
id | pubmed-6589776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-65897762019-07-15 PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation Haghandish, Nasim Baldwin, R. Mitchell Morettin, Alan Dawit, Haben Tesfu Adhikary, Hemanta Masson, Jean-Yves Mazroui, Rachid Trinkle-Mulcahy, Laura Côté, Jocelyn Mol Biol Cell Articles Protein arginine methyltransferases (PRMTs) are a family of enzymes that modify proteins by methylating the guanidino nitrogen atoms of arginine residues to regulate cellular processes such as chromatin remodeling, pre-mRNA splicing, and signal transduction. PRMT7 is the single type III PRMT solely capable of arginine monomethylation. To date, other than histone proteins, there are very few identified substrates of PRMT7. We therefore performed quantitative mass spectrometry experiments to identify PRMT7’s interactome and potential substrates to better characterize the enzyme’s biological function(s) in cells. These experiments revealed that PRMT7 interacts with and can methylate eukaryotic translation initiation factor 2 alpha (eIF2α), in vitro and in breast cancer cells. Furthermore, we uncovered a potential regulatory interplay between eIF2α arginine methylation by PRMT7 and stress-induced phosphorylation status of eIF2α at serine 51. Finally, we demonstrated that PRMT7 is required for eIF2α-dependent stress granule formation in the face of various cellular stresses. Altogether, our findings implicate PRMT7 as a novel mediator of eIF2α-dependent cellular stress response pathways. The American Society for Cell Biology 2019-03-15 /pmc/articles/PMC6589776/ /pubmed/30699057 http://dx.doi.org/10.1091/mbc.E18-05-0330 Text en © 2019 Haghandish et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Haghandish, Nasim Baldwin, R. Mitchell Morettin, Alan Dawit, Haben Tesfu Adhikary, Hemanta Masson, Jean-Yves Mazroui, Rachid Trinkle-Mulcahy, Laura Côté, Jocelyn PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation |
title | PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation |
title_full | PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation |
title_fullStr | PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation |
title_full_unstemmed | PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation |
title_short | PRMT7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation |
title_sort | prmt7 methylates eukaryotic translation initiation factor 2α and regulates its role in stress granule formation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589776/ https://www.ncbi.nlm.nih.gov/pubmed/30699057 http://dx.doi.org/10.1091/mbc.E18-05-0330 |
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