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 (Swi1_1–32) can decorate [SWI⁺] aggregation and stably maintain and transmit [SWI⁺] independently of full-length Swi1. Regions smaller than Swi1_1–32 are either incapable of aggregation or unstably propagate [SWI⁺]. When fused to Sup35MC, the [PSI⁺] determinant lacking its PrD, Swi1_1–31 and Swi1_1–32 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.

KEYWORDS:

• protein aggregation
• amyloids
• prion
• epigenetic inheritance
• Saccharomyces cerevisiae
• yeast
• Swi1
• SWI/SNF
• prion domain (PrD)
• prion domain
• prions
• yeasts

ACKNOWLEDGMENTS

We thank Y. O. Chernoff (Georgia Institute of Technology). J. S. Weissman (University of California, San Francisco), and Susan Liebman (University of Nevada, Reno) for plasmids, yeast strains, and antibodies, as well as D. K. Goncharoff for manuscript editing and critical comments.

This work was supported by grants from the National Institutes of Health (grant 1 R01 GM110045) to L.L., the National Science Foundation (grant 1122135) to L.L., and the National Institute of Aging (grant T32 AG220506) to S.V.

The funders had no role in the study design, data collection and interpretation, or decision to submit the work for publication.