Modification of tRNALys UUU by Elongator Is Essential for Efficient Translation of Stress mRNAs

Fernández Vázquez, Jorge; Vargas Pérez, Itzel; Sansó Martínez, Miriam, 1979-; Buhne, Karin; Carmona, Mercè; Paulo Mirasol, Esther, 1984-; Hermand, Damien; Rodríguez Gabriel, Miguel; Ayté del Olmo, José; Leidel, Sebastian; Hidalgo Hernando, Elena

Modification of tRNALys UUU by Elongator Is Essential for Efficient Translation of Stress mRNAs

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dc.contributor.author Fernández Vázquez, Jorgeca
dc.contributor.author Vargas Pérez, Itzelca
dc.contributor.author Sansó Martínez, Miriam, 1979-ca
dc.contributor.author Buhne, Karinca
dc.contributor.author Carmona, Mercèca
dc.contributor.author Paulo Mirasol, Esther, 1984-ca
dc.contributor.author Hermand, Damienca
dc.contributor.author Rodríguez Gabriel, Miguelca
dc.contributor.author Ayté del Olmo, Joséca
dc.contributor.author Leidel, Sebastianca
dc.contributor.author Hidalgo Hernando, Elenaca
dc.date.accessioned 2015-04-20T07:05:28Z
dc.date.available 2015-04-20T07:05:28Z
dc.date.issued 2013ca
dc.description.abstract 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 H2O2. In particular, a plasmid over-expressing the tRNALysUUU complements the stress-related phenotypes of Sin3/Elp3 mutant cells. We have determined that the main H2O2-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.en
dc.description.sponsorship This work was supported by the Spanish Ministry of Science and Innovation (BFU2009-06933 and BFU2012-32045), PLAN E and FEDER, by the Spanish program Consolider-Ingenio 2010 Grant CSD 2007-0020, and by SGR2009-196 from Generalitat de Catalunya (Spain) to EH. EH and JA are recipients of ICREA Academia Awards (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.format.mimetype application/pdfca
dc.identifier.citation Fernandez-Vazquez J, Vargas-Perez I, Sanso M, Buhne K, Carmona M, Paulo E et al. Modification of tRNALys UUU by Elongator Is Essential for Efficient Translation of Stress mRNAs. PLoS Genetics. 2013;9(7):e1003467. DOI: 10.1371/journal.pgen.1003647ca
dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1003647
dc.identifier.issn 1553-7390ca
dc.identifier.uri http://hdl.handle.net/10230/23443
dc.language.iso engca
dc.publisher Public Library of Science (PLoS)ca
dc.relation.ispartof PLoS Genetics. 2013;9(7):e1003467
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-06933
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-32045
dc.rights © Fernández-Vázquez et al. 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 credited
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other RNA missatgerca
dc.subject.other Schizosaccharomyces pombe -- Metabolismeca
dc.subject.other Histonesca
dc.title Modification of tRNALys UUU by Elongator Is Essential for Efficient Translation of Stress mRNAsen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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