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Modification of tRNA(Lys) (UUU) by Elongator Is Essential for Efficient Translation of Stress mRNAs
The Elongator complex, including the histone acetyl transferase Sin3/Elp3, was isolated as an RNA polymerase II-interacting complex, and cells deficient in Elongator subunits display transcriptional defects. However, it has also been shown that Elongator mediates the modification of some tRNAs, modu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715433/ https://www.ncbi.nlm.nih.gov/pubmed/23874237 http://dx.doi.org/10.1371/journal.pgen.1003647 |
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author | Fernández-Vázquez, Jorge Vargas-Pérez, Itzel Sansó, Miriam Buhne, Karin Carmona, Mercè Paulo, Esther Hermand, Damien Rodríguez-Gabriel, Miguel Ayté, José Leidel, Sebastian Hidalgo, Elena |
author_facet | Fernández-Vázquez, Jorge Vargas-Pérez, Itzel Sansó, Miriam Buhne, Karin Carmona, Mercè Paulo, Esther Hermand, Damien Rodríguez-Gabriel, Miguel Ayté, José Leidel, Sebastian Hidalgo, Elena |
author_sort | Fernández-Vázquez, Jorge |
collection | PubMed |
description | The Elongator complex, including the histone acetyl transferase Sin3/Elp3, was isolated as an RNA polymerase II-interacting complex, and cells deficient in Elongator subunits display transcriptional defects. However, it has also been shown that Elongator mediates the modification of some tRNAs, modulating translation efficiency. We show here that the fission yeast Sin3/Elp3 is important for oxidative stress survival. The stress transcriptional program, governed by the Sty1-Atf1-Pcr1 pathway, is affected in mutant cells, but not severely. On the contrary, cells lacking Sin3/Elp3 cannot modify the uridine wobble nucleoside of certain tRNAs, and other tRNA modifying activities such as Ctu1-Ctu2 are also essential for normal tolerance to H(2)O(2). In particular, a plasmid over-expressing the tRNA(Lys) (UUU) complements the stress-related phenotypes of Sin3/Elp3 mutant cells. We have determined that the main H(2)O(2)-dependent genes, including those coding for the transcription factors Atf1 and Pcr1, are highly expressed mRNAs containing a biased number of lysine-coding codons AAA versus AAG. Thus, their mRNAs are poorly translated after stress in cells lacking Sin3/Elp3 or Ctu2, whereas a mutated atf1 transcript with AAA-to-AAG lysine codons is efficiently translated in all strain backgrounds. Our study demonstrates that the lack of a functional Elongator complex results in stress phenotypes due to its contribution to tRNA modification and subsequent translation inefficiency of certain stress-induced, highly expressed mRNAs. These results suggest that the transcriptional defects of these strain backgrounds may be a secondary consequence of the deficient expression of a transcription factor, Atf1-Pcr1, and other components of the transcriptional machinery. |
format | Online Article Text |
id | pubmed-3715433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37154332013-07-19 Modification of tRNA(Lys) (UUU) by Elongator Is Essential for Efficient Translation of Stress mRNAs Fernández-Vázquez, Jorge Vargas-Pérez, Itzel Sansó, Miriam Buhne, Karin Carmona, Mercè Paulo, Esther Hermand, Damien Rodríguez-Gabriel, Miguel Ayté, José Leidel, Sebastian Hidalgo, Elena PLoS Genet Research Article The Elongator complex, including the histone acetyl transferase Sin3/Elp3, was isolated as an RNA polymerase II-interacting complex, and cells deficient in Elongator subunits display transcriptional defects. However, it has also been shown that Elongator mediates the modification of some tRNAs, modulating translation efficiency. We show here that the fission yeast Sin3/Elp3 is important for oxidative stress survival. The stress transcriptional program, governed by the Sty1-Atf1-Pcr1 pathway, is affected in mutant cells, but not severely. On the contrary, cells lacking Sin3/Elp3 cannot modify the uridine wobble nucleoside of certain tRNAs, and other tRNA modifying activities such as Ctu1-Ctu2 are also essential for normal tolerance to H(2)O(2). In particular, a plasmid over-expressing the tRNA(Lys) (UUU) complements the stress-related phenotypes of Sin3/Elp3 mutant cells. We have determined that the main H(2)O(2)-dependent genes, including those coding for the transcription factors Atf1 and Pcr1, are highly expressed mRNAs containing a biased number of lysine-coding codons AAA versus AAG. Thus, their mRNAs are poorly translated after stress in cells lacking Sin3/Elp3 or Ctu2, whereas a mutated atf1 transcript with AAA-to-AAG lysine codons is efficiently translated in all strain backgrounds. Our study demonstrates that the lack of a functional Elongator complex results in stress phenotypes due to its contribution to tRNA modification and subsequent translation inefficiency of certain stress-induced, highly expressed mRNAs. These results suggest that the transcriptional defects of these strain backgrounds may be a secondary consequence of the deficient expression of a transcription factor, Atf1-Pcr1, and other components of the transcriptional machinery. Public Library of Science 2013-07-18 /pmc/articles/PMC3715433/ /pubmed/23874237 http://dx.doi.org/10.1371/journal.pgen.1003647 Text en © 2013 Fernández-Vázquez et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Fernández-Vázquez, Jorge Vargas-Pérez, Itzel Sansó, Miriam Buhne, Karin Carmona, Mercè Paulo, Esther Hermand, Damien Rodríguez-Gabriel, Miguel Ayté, José Leidel, Sebastian Hidalgo, Elena Modification of tRNA(Lys) (UUU) by Elongator Is Essential for Efficient Translation of Stress mRNAs |
title | Modification of tRNA(Lys)
(UUU) by Elongator Is Essential for Efficient Translation of Stress mRNAs |
title_full | Modification of tRNA(Lys)
(UUU) by Elongator Is Essential for Efficient Translation of Stress mRNAs |
title_fullStr | Modification of tRNA(Lys)
(UUU) by Elongator Is Essential for Efficient Translation of Stress mRNAs |
title_full_unstemmed | Modification of tRNA(Lys)
(UUU) by Elongator Is Essential for Efficient Translation of Stress mRNAs |
title_short | Modification of tRNA(Lys)
(UUU) by Elongator Is Essential for Efficient Translation of Stress mRNAs |
title_sort | modification of trna(lys)
(uuu) by elongator is essential for efficient translation of stress mrnas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715433/ https://www.ncbi.nlm.nih.gov/pubmed/23874237 http://dx.doi.org/10.1371/journal.pgen.1003647 |
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