Newly identified prions in budding yeast, and their possible functions

Abstract

Yeast prions are atypical genetic elements that are transmitted as heritable protein conformations. [PSI+], [URE3], and [PIN+] are three well-studied prions in the budding yeast, Saccharomyces cerevisiae. In the last three years, several additional prions have been reported in yeast, including [SWI+], [OCT+], [MCA], [GAR+], [MOT3+], [ISP+], and [NSI+]. The growing number of yeast prions suggests that protein-based inheritance might be a widespread biological phenomenon. In this review, we summarize the characteristics of each prion element, and discuss their potential functional roles in yeast biology.

Figure 1

Postulated mechanisms for prion-mediated transcriptional regulation. A, A titration model shows that [URE3] formation leads to DAL5 activation due to Ure2 insufficiency. In [ureo] cells, Ure2 binds to the DAL5 activator Gln3 and as a consequence, DAL5 promoter is off. B, [SWI⁺] formation can lead to the destruction of SWI/SNF complex assembly and/or formation of Swi1-free SWI/SNF sub-complexes to further modulate gene expression. C, An antagonism model shows that formation of [SWI⁺] or [OCT⁺] can have opposite effects on FLO1 expression.

Figure 2

Three prions, [PSI⁺], [ISP⁺], and [NSI⁺], affect translation fidelity. A, In [PSI⁺] cells, the majority of Sup35 is sequestered in prion aggregates, resulting in partial read-through of nonsense translation codons, such as TGA in ade1-14. B, In [ISP⁺] cells, Sfp1 forms nuclear prion aggregates that result in suppression of nonsense read-through in some sup35 and sup45 mutant strains. C, In [NSI⁺] cells, an unidentified prion protein forms prion aggregates, resulting in nonsense codon read-through, a phenotype similar to that of [PSI⁺]. Aggregated Sup35 is not implicated in this phenotype.