A non-Q/N-rich prion domain of a foreign prion, [Het-s], can propagate as a prion in yeast
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Updated: Jul 13, 2026

High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Vibha Taneja1, Marie-Lise Maddelein, Nicolas Talarek
1Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Abstract:
Prions are self-propagating, infectious aggregates of misfolded proteins. The mammalian prion, PrP(Sc), causes fatal neurodegenerative disorders. Fungi also have prions. While yeast prions depend upon glutamine/asparagine (Q/N)-rich regions, the Podospora anserina HET-s and PrP prion proteins lack such sequences. Nonetheless, we show that the HET-s prion domain fused to GFP propagates as a prion in yeast. Analogously to native yeast prions, transient overexpression of the HET-s fusion induces ring-like aggregates that propagate in daughter cells as cytoplasmically inherited, detergent-resistant dot aggregates. Efficient dot propagation, but not ring formation, is dependent upon the Hsp104 chaperone. The yeast prion [PIN(+)] enhances HET-s ring formation, suggesting that prions with and without Q/N-rich regions interact. Finally, HET-s aggregates propagated in yeast are infectious when introduced into Podospora. Taken together, these results demonstrate prion propagation in a truly foreign host. Since yeast can host non-Q/N-rich prions, such native yeast prions may exist.
Insights
Fungal prion proteins, HET-s, can propagate in yeast, a foreign host, even without Q/N-rich regions. These yeast-propagated prions are infectious in their native fungal host.
Area of Science:
- Protein misfolding and aggregation
- Prion biology
- Fungal genetics
Background:
- Prions are infectious proteins causing neurodegenerative diseases.
- Yeast prions typically require Q/N-rich domains for propagation.
- Fungal prion proteins like HET-s lack these Q/N-rich regions.
Purpose of the Study:
- To investigate if non-Q/N-rich fungal prions can propagate in yeast.
- To determine if yeast-hosted fungal prions retain infectivity.
- To explore interactions between different prion types.
Main Methods:
- Fusion of the HET-s prion domain to Green Fluorescent Protein (GFP).
- Transient overexpression in yeast to induce prion formation.
- Analysis of aggregate morphology (ring-like and dot structures).
- Assessing dependence on the Hsp104 chaperone.
- Testing infectivity of yeast-propagated prions in Podospora.
Main Results:
- HET-s-GFP fusion protein successfully propagated as a prion in yeast.
- Propagation involved ring-like aggregates upon induction and dot aggregates in daughter cells.
- Dot propagation, but not ring formation, required the Hsp104 chaperone.
- [PIN(+)] yeast prion enhanced HET-s ring formation, indicating cross-prion interaction.
- HET-s aggregates propagated in yeast were infectious in Podospora.
Conclusions:
- Yeast can host prions lacking Q/N-rich domains, expanding the known host range for prions.
- Prions with and without Q/N-rich regions can interact within the same cell.
- This study demonstrates prion propagation in a heterologous host and suggests the potential existence of native non-Q/N-rich yeast prions.
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