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Updated: Jun 15, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Analyzing the birth and propagation of two distinct prions, [PSI+] and [Het-s](y), in yeast
Vidhu Mathur1, Vibha Taneja, Yidi Sun
1Department of Biological Sciences, University of Illinois, Chicago, IL 60607, USA.
Abstract:
Various proteins, like the infectious yeast prions and the noninfectious human Huntingtin protein (with expanded polyQ), depend on a Gln or Asn (QN)-rich region for amyloid formation. Other prions, e.g., mammalian PrP and the [Het-s] prion of Podospora anserina, although still able to form infectious amyloid aggregates, do not have QN-rich regions. Furthermore, [Het-s] and yeast prions appear to differ dramatically in their amyloid conformation. Despite these differences, a fusion of the Het-s prion domain to GFP (Het-sPrD-GFP) can propagate in yeast as a prion called [Het-s](y). We analyzed the properties of two divergent prions in yeast: [Het-s](y) and the native yeast prion [PSI(+)] (prion form of translational termination factor Sup35). Curiously, the induced appearance and transmission of [PSI(+)] and [Het-s](y) aggregates is remarkably similar. Overexpression of tagged prion protein (Sup35-GFP or Het-sPrD-GFP) in nonprion cells gives rise to peripheral, and later internal, ring/mesh-like aggregates. The cells with these ring-like aggregates give rise to daughters with one (perivacuolar) or two (perivacuolar and juxtanuclear) dot-like aggregates per cell. These line, ring, mesh, and dot aggregates are not really the transmissible prion species and should only be regarded as phenotypic markers of the presence of the prions. Both [PSI(+)] and [Het-s](y) first appear in daughters as numerous tiny dot-like aggregates, and both require the endocytic protein, Sla2, for ring formation, but not propagation.
Insights
Two yeast prions, [PSI(+)] and [Het-s](y), share similar aggregate formation pathways, requiring the Sla2 protein for initial ring formation but not for prion propagation.
Area of Science:
- Biochemistry
- Molecular Biology
- Yeast Genetics
Background:
- Prions are infectious proteins that can form amyloid aggregates.
- Some prions, like yeast prion [PSI(+)] and human Huntingtin protein, rely on Gln/Asn-rich regions for amyloid formation.
- Other prions, such as mammalian PrP and [Het-s], lack these QN-rich regions but still form infectious aggregates, exhibiting distinct conformations.
Purpose of the Study:
- To compare the aggregation properties of two divergent prions in yeast: the native [PSI(+)] prion and the engineered [Het-s](y) prion.
- To investigate the similarities and differences in the de novo appearance and transmission of these prions.
- To identify cellular factors involved in prion aggregate formation.
Main Methods:
- Overexpression of tagged prion proteins (Sup35-GFP and Het-sPrD-GFP) in nonprion yeast cells.
- Microscopic analysis of aggregate formation and cellular localization.
- Genetic analysis involving the endocytic protein Sla2.
Main Results:
- Both [PSI(+)] and [Het-s](y) prions exhibit similar patterns of aggregate formation, starting as peripheral, then internal, ring/mesh-like structures.
- Cells with these initial aggregates produce daughter cells with distinct dot-like aggregates (perivacuolar and/or juxtanuclear).
- The formation of ring-like aggregates requires the endocytic protein Sla2, but Sla2 is not essential for prion propagation.
Conclusions:
- Despite differing origins and sequences, [PSI(+)] and [Het-s](y) prions utilize similar cellular pathways for initial aggregate formation in yeast.
- The observed aggregate structures (lines, rings, meshes, dots) are phenotypic markers, not the transmissible prion species themselves.
- Sla2 plays a role in the early stages of prion seeding or stabilization, specifically in ring formation, but is dispensable for subsequent prion transmission.
