[NSI +] determinant has a pleiotropic phenotypic manifestation that is modulated by SUP35, SUP45, and VTS1 genes
We recently discovered the novel non-chromosomal determinant in Saccharomyces cerevisiae [NSI +] (nonsense suppression inducer), which causes omnipotent nonsense suppression in strains where the Sup35 N-terminal domain is deleted. [NSI +] possesses yeast prion features and does not correspond to previously identified yeast prion determinants. Here, we show that [NSI + ] enhances nonsense codon read-through and inhibits vegetative growth in S. cerevisiae. Using a large-scale overexpression screen to identify genes that impact the phenotypic effects of [NSI +], we found that the SUP35 and SUP45 genes encoding the translation termination factors eRF3 and eRF1, respectively, modulate nonsense suppression in [NSI +] strains. The VTS1 gene encodes an NQ-enriched RNA-binding protein that enhances nonsense suppression in [NSI +] and [nsi −] strains. We demonstrate that VTS1 overexpression, like [NSI +] induction, causes translational read-through and growth defects in S. cerevisiae.
KeywordsYeast [NSI+] Prion SUP35 SUP45 VTS1
We are grateful to E. Andreeva for technical assistance. We thank Y. Chernoff, A. Borchsenius, Y. Pavlov, and M. Ter-Avanesyan for kindly providing plasmids, A. Tomilin for helping with luminometer, and S. Chabelskaya for kindly gifting anti-Sup45 antibodies. This work was supported by Grants of Russian Foundation for Basic Research 10-04-00395-a to A. P. G, Program of Presidium of the Russian Academy of Science “Basic Sciences for Medicine” 08-12 to S. G. I.-V., Federal Grant-in-Aid Program “Human Capital for Science and Education in Innovative Russia” (Governmental Contract P1354), and St. Petersburg Governmental Grant 2.6/16-05/291-A for Ph.D. students to A. A. N. The authors acknowledge the Saint-Petersburg University for a research grant.
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