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Functional interplay between protein arginine methyltransferases in Trypanosoma brucei
Arginine methylation is a common posttranslational modification that has far-reaching cellular effects. Trypanosoma brucei is an early-branching eukaryote with four characterized protein arginine methyltransferases (PRMTs), one additional putative PRMT, and over 800 arginine methylated proteins, sug...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234254/ https://www.ncbi.nlm.nih.gov/pubmed/25044453 http://dx.doi.org/10.1002/mbo3.191 |
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author | Lott, Kaylen Zhu, Lu Fisk, John C Tomasello, Danielle L Read, Laurie K |
author_facet | Lott, Kaylen Zhu, Lu Fisk, John C Tomasello, Danielle L Read, Laurie K |
author_sort | Lott, Kaylen |
collection | PubMed |
description | Arginine methylation is a common posttranslational modification that has far-reaching cellular effects. Trypanosoma brucei is an early-branching eukaryote with four characterized protein arginine methyltransferases (PRMTs), one additional putative PRMT, and over 800 arginine methylated proteins, suggesting that arginine methylation has widespread impacts in this organism. While much is known about the activities of individual T. brucei PRMTs (TbPRMTs), little is known regarding how TbPRMTs function together in vivo. In this study, we analyzed single and selected double TbPRMT knockdowns for the impact on expression of TbPRMTs and global methylation status. Repression of TbPRMT1 caused a decrease in asymmetric dimethylarginine and a marked increase in monomethylarginine that was catalyzed by TbPRMT7, suggesting that TbPRMT1 and TbPRMT7 can compete for the same substrate. We also observed an unexpected and strong interdependence between TbPRMT1 and TbPRMT3 protein levels. This finding, together with the observation of similar methyl landscape profiles in TbPRMT1 and TbPRMT3 repressed cells, strongly suggests that these two enzymes form a functional complex. We show that corepression of TbPRMT6/7 synergistically impacts growth of procyclic-form T. brucei. Our findings also implicate the actions of noncanonical, and as yet unidentified, PRMTs in T. brucei. Together, our studies indicate that TbPRMTs display a functional interplay at multiple levels. |
format | Online Article Text |
id | pubmed-4234254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-42342542014-12-04 Functional interplay between protein arginine methyltransferases in Trypanosoma brucei Lott, Kaylen Zhu, Lu Fisk, John C Tomasello, Danielle L Read, Laurie K Microbiologyopen Original Research Arginine methylation is a common posttranslational modification that has far-reaching cellular effects. Trypanosoma brucei is an early-branching eukaryote with four characterized protein arginine methyltransferases (PRMTs), one additional putative PRMT, and over 800 arginine methylated proteins, suggesting that arginine methylation has widespread impacts in this organism. While much is known about the activities of individual T. brucei PRMTs (TbPRMTs), little is known regarding how TbPRMTs function together in vivo. In this study, we analyzed single and selected double TbPRMT knockdowns for the impact on expression of TbPRMTs and global methylation status. Repression of TbPRMT1 caused a decrease in asymmetric dimethylarginine and a marked increase in monomethylarginine that was catalyzed by TbPRMT7, suggesting that TbPRMT1 and TbPRMT7 can compete for the same substrate. We also observed an unexpected and strong interdependence between TbPRMT1 and TbPRMT3 protein levels. This finding, together with the observation of similar methyl landscape profiles in TbPRMT1 and TbPRMT3 repressed cells, strongly suggests that these two enzymes form a functional complex. We show that corepression of TbPRMT6/7 synergistically impacts growth of procyclic-form T. brucei. Our findings also implicate the actions of noncanonical, and as yet unidentified, PRMTs in T. brucei. Together, our studies indicate that TbPRMTs display a functional interplay at multiple levels. BlackWell Publishing Ltd 2014-10 2014-07-07 /pmc/articles/PMC4234254/ /pubmed/25044453 http://dx.doi.org/10.1002/mbo3.191 Text en © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Lott, Kaylen Zhu, Lu Fisk, John C Tomasello, Danielle L Read, Laurie K Functional interplay between protein arginine methyltransferases in Trypanosoma brucei |
title | Functional interplay between protein arginine methyltransferases in Trypanosoma brucei |
title_full | Functional interplay between protein arginine methyltransferases in Trypanosoma brucei |
title_fullStr | Functional interplay between protein arginine methyltransferases in Trypanosoma brucei |
title_full_unstemmed | Functional interplay between protein arginine methyltransferases in Trypanosoma brucei |
title_short | Functional interplay between protein arginine methyltransferases in Trypanosoma brucei |
title_sort | functional interplay between protein arginine methyltransferases in trypanosoma brucei |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234254/ https://www.ncbi.nlm.nih.gov/pubmed/25044453 http://dx.doi.org/10.1002/mbo3.191 |
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