Aufsatz in einer Fachzeitschrift
Loss of anticodon wobble uridine modifications affects tRNALys function and protein levels in Saccharomyces cerevisiae



Details zur Publikation
Autor(inn)en:
Klassen, R.; Grunewald, P.; Thüring, K.; Eichler, C.; Helm, M.; Schaffrath, R.
Publikationsjahr:
2015
Zeitschrift:
PLOS ONE
Seitenbereich:
e0119261
Jahrgang/Band:
11/2015
ISSN:
1932-6203

Zusammenfassung, Abstract
In eukaryotes, wobble uridines in the anticodons of tRNALysUUU, tRNAGluUUCand tRNAGlnUUGare modified to 5-methoxy-carbonyl-methyl-2-thio-uridine (mcm5s2U). While mutations in subunits of the Elongator complex (Elp1-Elp6), which disable mcm5side 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 onSaccharomyces cerevisiae. Contrary to such absolute requirement of mcm5s2U for viability, we demonstrate here that in theS.cerevisiaeS288C-derived background, both pathways can be simultaneously inactivated, resulting in combined loss of tRNA anticodon modifications (mcm5U and s2U) without a lethal effect. However, anelp3disruption strain displays synthetic sick interaction and synergistic temperature sensitivity when combined with eitheruba4orurm1mutations, suggesting major translational defects in the absence of mcm5s2U modifications. Consistent with this notion, we find cellular protein levels drastically decreased in anelp3uba4double 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 mcm5and s2wobble uridine modification that could account for growth impairment and mainly originates from tRNALysUUUhypomodification and malfunction.


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Zuletzt aktualisiert 2019-25-07 um 19:12

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