Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications

Abstract Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications of tRNAs. In higher eukaryotes, these processes are important for preventing neurological and developmental defects and cancer. In this study, w...

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Autores principales:	Desirée Villahermosa, Oliver Fleck
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/11def878f1554a639386e93c7213cc02
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spelling	oai:doaj.org-article:11def878f1554a639386e93c7213cc022021-12-02T16:08:09ZElp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications10.1038/s41598-017-07647-12045-2322https://doaj.org/article/11def878f1554a639386e93c7213cc022017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07647-1https://doaj.org/toc/2045-2322Abstract Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications of tRNAs. In higher eukaryotes, these processes are important for preventing neurological and developmental defects and cancer. In this study, we used Schizosaccharomyces pombe as a model to analyse mutants defective in eEF2 modification (dph1Δ), in tRNA modifications (elp3Δ), or both (dph3Δ) for sensitivity to cytotoxic agents and thermal stress. The dph3Δ and elp3Δ mutants were sensitive to a range of drugs and had growth defects at low temperature. dph3Δ was epistatic with dph1Δ for sensitivity to hydroxyurea and methyl methanesulfonate, and with elp3Δ for methyl methanesulfonate and growth at 16 °C. The dph1Δ and dph3Δ deletions rescued growth defects of elp3Δ in response to thiabendazole and at 37 °C. Elevated tRNALys UUU levels suppressed the elp3Δ phenotypes and some of the dph3Δ phenotypes, indicating that lack of tRNALys UUU modifications were responsible. Furthermore, we found positive genetic interactions of elp3Δ and dph3Δ with sty1Δ and atf1Δ, indicating that Elp3/Dph3-dependent tRNA modifications are important for efficient biosynthesis of key factors required for accurate responses to cytotoxic stress conditions.Desirée VillahermosaOliver FleckNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Desirée Villahermosa Oliver Fleck Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications
description	Abstract Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications of tRNAs. In higher eukaryotes, these processes are important for preventing neurological and developmental defects and cancer. In this study, we used Schizosaccharomyces pombe as a model to analyse mutants defective in eEF2 modification (dph1Δ), in tRNA modifications (elp3Δ), or both (dph3Δ) for sensitivity to cytotoxic agents and thermal stress. The dph3Δ and elp3Δ mutants were sensitive to a range of drugs and had growth defects at low temperature. dph3Δ was epistatic with dph1Δ for sensitivity to hydroxyurea and methyl methanesulfonate, and with elp3Δ for methyl methanesulfonate and growth at 16 °C. The dph1Δ and dph3Δ deletions rescued growth defects of elp3Δ in response to thiabendazole and at 37 °C. Elevated tRNALys UUU levels suppressed the elp3Δ phenotypes and some of the dph3Δ phenotypes, indicating that lack of tRNALys UUU modifications were responsible. Furthermore, we found positive genetic interactions of elp3Δ and dph3Δ with sty1Δ and atf1Δ, indicating that Elp3/Dph3-dependent tRNA modifications are important for efficient biosynthesis of key factors required for accurate responses to cytotoxic stress conditions.
format	article
author	Desirée Villahermosa Oliver Fleck
author_facet	Desirée Villahermosa Oliver Fleck
author_sort	Desirée Villahermosa
title	Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications
title_short	Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications
title_full	Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications
title_fullStr	Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications
title_full_unstemmed	Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications
title_sort	elp3 and dph3 of schizosaccharomyces pombe mediate cellular stress responses through trnalys uuu modifications
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/11def878f1554a639386e93c7213cc02
work_keys_str_mv	AT desireevillahermosa elp3anddph3ofschizosaccharomycespombemediatecellularstressresponsesthroughtrnalysuuumodifications AT oliverfleck elp3anddph3ofschizosaccharomycespombemediatecellularstressresponsesthroughtrnalysuuumodifications
_version_	1718384577213366272

Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALys UUU modifications

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