Loss of anticodon wobble uridine modifications affects tRNA(Lys) function and protein levels in Saccharomyces cerevisiae

PloS One
Roland KlassenRaffael Schaffrath

Abstract

In eukaryotes, wobble uridines in the anticodons of tRNA(Lys)UUU, tRNA(Glu)UUC and tRNA(Gln)UUG are modified to 5-methoxy-carbonyl-methyl-2-thio-uridine (mcm5s2U). While mutations in subunits of the Elongator complex (Elp1-Elp6), which disable mcm5 side chain formation, or removal of components of the thiolation pathway (Ncs2/Ncs6, Urm1, Uba4) are individually tolerated, the combination of both modification defects has been reported to have lethal effects on Saccharomyces cerevisiae. Contrary to such absolute requirement of mcm5s2U for viability, we demonstrate here that in the S. cerevisiae S288C-derived background, both pathways can be simultaneously inactivated, resulting in combined loss of tRNA anticodon modifications (mcm5U and s2U) without a lethal effect. However, an elp3 disruption strain displays synthetic sick interaction and synergistic temperature sensitivity when combined with either uba4 or urm1 mutations, suggesting major translational defects in the absence of mcm5s2U modifications. Consistent with this notion, we find cellular protein levels drastically decreased in an elp3uba4 double mutant and show that this effect as well as growth phenotypes can be partially rescued by excess of tRNA(Lys)UUU. These results...Continue Reading

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Citations

Jun 24, 2016·Translation·Namit Ranjan, Marina V Rodnina
Apr 21, 2016·Cellular and Molecular Life Sciences : CMLS·Markus DuechlerBarbara Nawrot
Mar 10, 2017·RNA Biology·Raffael Schaffrath, Sebastian A Leidel
Aug 9, 2016·Nucleic Acids Research·Roland KlassenRaffael Schaffrath
Jul 31, 2018·FEBS Letters·Shawn M LyonsPavel Ivanov
Oct 6, 2018·Molecular Systems Biology·Chee Sheng NgPeter R Preiser
Aug 30, 2020·Current Genetics·Roland KlassenRaffael Schaffrath
Nov 17, 2016·Frontiers in Molecular Neuroscience·Marija Kojic, Brandon Wainwright
Mar 28, 2019·Nucleic Acids Research·Rościsław KrutyhołowaSebastian Glatt
Nov 30, 2019·Current Genetics·Fu XuMarcus J O Johansson
May 12, 2019·Plant & Cell Physiology·Yumi NakaiTakato Yano
Jan 31, 2017·Biomolecules·Roland Klassen, Raffael Schaffrath
Oct 27, 2018·Genes·Alexander BruchRaffael Schaffrath
Nov 28, 2018·International Journal of Molecular Sciences·Marisa PereiraAna Raquel Soares
Jun 3, 2020·Nucleic Acids Research·Alexander BruchRoland Klassen
Aug 26, 2018·Scientific Reports·Roland Klassen, Raffael Schaffrath
Dec 12, 2018·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Jillian Ramos, Dragony Fu
Apr 22, 2021·Science China. Life Sciences·Jing LiRu-Juan Liu
Aug 28, 2021·International Journal of Molecular Sciences·Bahar KhonsariRaffael Schaffrath

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Methods Mentioned

BETA
aminoacylation
PCR

Software Mentioned

Agilent MassHunter Analysis
Agilent MassHunter
CellSens

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