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2015Metadata
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Artikel (Publikationen im Open Access gefördert durch die UB)
Loss of Anticodon Wobble Uridine Modifications Affects tRNALys Function and Protein Levels in Saccharomyces cerevisiae
Zusammenfassung
In eukaryotes, wobble uridines in the anticodons of tRNALysUUU, tRNAGluUUC and tRNAGlnUUG 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 tRNALysUUU. These results may indicate a global translational or protein homeostasis defect in cells simultaneously lacking mcm5 and s2 wobble uridine modification that could account for growth impairment and mainly originates from tRNALysUUU hypomodification and malfunction.
Förderhinweis
Gefördert durch den Publikationsfonds der Universität KasselSammlung(en)
Publikationen (Fachgebiet Mikrobiologie)Artikel (Publikationen im Open Access gefördert durch die UB)
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@article{urn:nbn:de:hebis:34-2015031347703,
author={Klassen, Roland and Grunewald, Pia and Thüring, Kathrin L. and Eichler, Christian and Helm, Mark and Schaffrath, Raffael},
title={Loss of Anticodon Wobble Uridine Modifications Affects tRNALys Function and Protein Levels in Saccharomyces cerevisiae},
year={2015}
}
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<resource xsi:schemaLocation="http://datacite.org/schema/kernel-2.2 http://schema.datacite.org/meta/kernel-2.2/metadata.xsd"> 2015-03-13T13:25:29Z 2015-03-13T13:25:29Z 2015 1932-6203 urn:nbn:de:hebis:34-2015031347703 http://hdl.handle.net/123456789/2015031347703 Gefördert durch den Publikationsfonds der Universität Kassel eng Urheberrechtlich geschützt https://rightsstatements.org/page/InC/1.0/ 570 Loss of Anticodon Wobble Uridine Modifications Affects tRNALys Function and Protein Levels in Saccharomyces cerevisiae Aufsatz In eukaryotes, wobble uridines in the anticodons of tRNALysUUU, tRNAGluUUC and tRNAGlnUUG 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 tRNALysUUU. These results may indicate a global translational or protein homeostasis defect in cells simultaneously lacking mcm5 and s2 wobble uridine modification that could account for growth impairment and mainly originates from tRNALysUUU hypomodification and malfunction. open access In: PLoS one. - Lawrence, Kan. : PLoS, 2015, 10 (3), e0119261, 1-17 Klassen, Roland Grunewald, Pia Thüring, Kathrin L. Eichler, Christian Helm, Mark Schaffrath, Raffael doi:10.1371/journal.pone.0119261 </resource>
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