Analysis of Small Critical Regions of Swi1 Conferring Prion Formation, Maintenance, and Transmission.

Abstract

Saccharomyces cerevisiae contains several prion elements, which are epigenetically transmitted as self-perpetuating protein conformations. One such prion is [SWI+ ], whose protein determinant is Swi1, a subunit of the SWI/SNF chromatin-remodeling complex. We previously reported that [SWI+ ] formation results in a partial loss-of-function phenotype of poor growth in nonglucose medium and abolishment of multicellular features. We also showed that the first 38 amino acids of Swi1 propagated [SWI+]. We show here that a region as small as the first 32 amino acids of Swi1 (Swi11-32) can decorate [SWI+] aggregation and stably maintain and transmit [SWI+] independently of full-length Swi1. Regions smaller than Swi11-32 are either incapable of aggregation or unstably propagate [SWI+]. When fused to Sup35MC, the [PSI+ ] determinant lacking its PrD, Swi11-31 and Swi11-32 can act as transferable prion domains (PrDs). The resulting fusions give rise to a novel chimeric prion, [SPS+], exhibiting [PSI+]-like nonsense suppression. Thus, an NH2-terminal region of ∼30 amino acids of Swi1 contains all the necessary information for in vivo prion formation, maintenance, and transmission. This PrD is unique in size and composition: glutamine free, asparagine rich, and the smallest defined to date. Our findings broaden our understanding of what features allow a protein region to serve as a PrD.