SUP35 expression is enhanced in yeast containing [ISP+], a prion form of the transcriptional regulator Sfp1

Abstract

[ISP+] is a prion form of the global transcriptional regulator Sfp1 in Saccharomyces cerevisiae that manifests phenotypically as an antisuppressor of specific sup35 nonsense suppressor mutations. Although SUP35 is a Sfp1 target, the mechanism of antisuppression is unclear. Here we show that the level of SUP35 transcription in [ISP+] cells containing the sup35 mutation is increased relative to [isp-] cells and cells with a SFP1 deletion. As a result, [ISP+] cells have increased amounts of Sup35 encoded by the mutant allele. Indeed, additional experiments showed that increased amounts of mutant Sup35 may cause antisuppression. Remarkably, [ISP+] effects are not equivalent to those produced by SFP1 deletion, so [ISP+] represents an obvious example of a functionally active prion form of a protein. This feature distinguishes [ISP+] from other yeast prions, where prion switch often has the same effect as inactivation of a prion host gene. We suggest that enhancement of SUP35 expression in [ISP+] cells is caused by specific interaction of Sfp1 in its prion form with some negative SUP35 regulator. We also demonstrate that the advantage of [ISP+] strains over [isp-] strains described in our earlier work is specific for certain genetic background and growth conditions.