SSD1suppresses phenotypes induced by the lack of Elongator-dependent tRNA modifications

Abstract

AbstractThe Elongator complex promotes formation of 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) side-chains on uridines at the wobble position of cytosolic eukaryotic tRNAs. In all eukaryotic organisms tested to date, the inactivation of Elongator not only leads to the lack of mcm5/ncm5groups in tRNAs, but also a wide variety of phenotypes. Although the phenotypes are most likely caused by a translational defect induced by reduced functionality of the hypomodified tRNAs, the mechanism(s) underlying individual phenotypes are poorly understood. In this study, we show that the genetic background modulates the phenotypes induced by the lack of mcm5/ncm5groups inSaccharomyces cerevisiae. We show that the stress-induced growth defects of Elongator mutants are stronger in the W303 than in the closely related S288C genetic background and that the phenotypic differences are caused by the known polymorphism at the locus for the mRNA binding protein Ssd1. Moreover, the mutantssd1allele found in W303 cells is required for the reported histone H3 acetylation and telomeric gene silencing defects of Elongator mutants. The difference at theSSD1locus also partially explains why the simultaneous lack of mcm5and 2-thio groups at wobble uridines is lethal in the W303 but not in the S288C background. Collectively, our results demonstrate that theSSD1locus modulates phenotypes induced by the lack of Elongator-dependent tRNA modifications.Author SummaryModified nucleosides in the anticodon region of tRNAs are important for the efficiency and fidelity of translation. The Elongator complex promotes formation of several related modified uridine residues at the wobble position of eukaryotic tRNAs. In yeast, plants, worms, mice and humans, mutations in genes for Elongator subunits lead to a wide variety of different phenotypes. Here, we show that the genetic background modulates the phenotypic consequences of the inactivation of budding yeast Elongator. This background effect is largely a consequence of a polymorphism at theSSD1locus, encoding a RNA binding protein that influences translation, stability and/or localization of mRNAs. We show that several phenotypes reported for yeast Elongator mutants are either significantly stronger or only detectable in strains harboring a mutantssd1allele. Thus,SSD1is a suppressor of the phenotypes induced by the hypomodification of tRNAs.