Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction

Zhiqiang Du*, Brandon Cho, Liming Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


(1) Background: Numerous prions exist in the budding yeast, including [SWI+], the prion form of Swi1—a subunit of the chromatin-remodeling complex SWI/SNF. Despite decades of research, the molecular mechanisms underlying prion initiation and propagation are not fully understood. In this study, we aimed to identify endogenous cellular proteins that destabilize [SWI+]. (2) Methods: We screened the MoBY-ORF 2.0 library for proteins that destabilize [SWI+] upon overproduction. We further explored the effects of the identified candidates against other yeast prions and analyzed their potential prion-curing mechanisms. (3) Results: Eighty-two [SWI+] suppressors were identified, and their effects were shown to be [SWI+]-specific. Interestingly, a few documented [SWI+] suppressors were not among the identified hits. Further experiments indicate that, for some of these [SWI+] suppressors, their overproduction, and thus their prion-curing activities, are regulated by environmental conditions. Bioinformatics analyses show that our identified [SWI+] suppressors are involved in diverse biological functions, with gene ontology term enrichments specifically for transcriptional regulation and translation. Competition for Swi1 monomers between [SWI+] and Swi1 interactors, including the SWI/SNF complex, is a potential prion-curing mechanism. (4) Conclusions: We identified a number of [SWI+]-specific suppressors that highlight unique features of [SWI+] in maintaining its self-perpetuating conformations.

Original languageEnglish (US)
Article number1366
Issue number7
StatePublished - Jul 2022


  • Saccharomyces cerevisiae
  • Swi1
  • [SWI]
  • prion inhibitors
  • prion propagation
  • protein aggregation
  • yeast

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology


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