[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.

[NSI (+)]: a novel non-Mendelian nonsense suppressor determinant in Saccharomyces cerevisiae.

Non-Mendelian determinants that control heritable traits in yeast are subdivided into two major groups-one that includes DNA- or RNA-based elements and another that comprises protein-based factors that are analogous to mammalian prion. All yeast non-Mendelian determinants show dominant inheritance, and some of them demonstrate cytoplasmic infectivity. Only prions, however, harbor-specific features, such as high frequency of induction following overproduction of prion-encoding protein, loss of the protein's normal function, and reversible curability. Here, we describe a novel nonchromosomal determinant that, in addition to [PSI (+)] and [ISP (+)], is involved in epigenetic control of nonsense suppression. This determinant, which we have designated [NSI (+)], causes nonsense suppression in the strains bearing the N-terminal-deleted or -modified SUP35 gene, but has no manifestation in the strains with the intact copy of SUP35. [NSI (+)] shows dominant non-Mendelian inheritance, reversible curability and may be transmitted by cytoduction, albeit with low frequency. Similar to yeast prions, this determinant can be cured by deletion or mutational inactivation of Hsp104. We have shown that [NSI (+)] does not correspond to the already identified yeast prions. Based on the data obtained, we hypothesize that [NSI (+)] is a novel prion factor involved in epigenetic control of nonsense suppression.