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Updated: May 17, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Expanding the yeast prion world: Active prion conversion of non-glutamine/asparagine-rich Mod5 for cell survival
Genjiro Suzuki1, Motomasa Tanaka
1Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Abstract:
Mammalian and fungal prion proteins form self-perpetuating β-sheet-rich fibrillar aggregates called amyloid. Prion inheritance is based on propagation of the regularly oriented amyloid structures of the prion proteins. All yeast prion proteins identified thus far contain aggregation-prone glutamine/asparagine (Gln/Asn)-rich domains, although the mammalian prion protein and fungal prion protein HET-s do not contain such sequences. In order to fill this gap, we searched for novel yeast prion proteins lacking Gln/Asn-rich domains via a genome-wide screen based on cross-seeding between two heterologous proteins and identified Mod5, a yeast tRNA isopentenyltransferase, as a novel non-Gln/Asn-rich yeast prion protein. Mod5 formed self-propagating amyloid fibers in vitro and the introduction of Mod5 amyloids into non-prion yeast induced dominantly and cytoplasmically heritable prion state [MOD (+) ], which harbors aggregates of endogenous Mod5. [MOD (+) ] yeast showed an increased level of membrane lipid ergosterol and acquired resistance to antifungal agents. Importantly, enhanced de novo formation of [MOD (+) ] was observed when non-prion yeast was grown under selective pressures from antifungal drugs. Our findings expand the family of yeast prions to non-Gln/Asn-rich proteins and reveal the acquisition of a fitness advantage for cell survival through active prion conversion.
Insights
Researchers discovered a new yeast prion protein, Mod5, which lacks typical Gln/Asn-rich domains. This prion confers antifungal resistance and enhances cell survival, expanding the known family of yeast prions.
Area of Science:
- Molecular Biology
- Prion Biology
- Yeast Genetics
Background:
- Prion proteins form self-perpetuating amyloid aggregates, crucial for prion inheritance.
- Known yeast prions possess glutamine/asparagine (Gln/Asn)-rich domains, unlike some mammalian and fungal prions.
- A gap existed in understanding yeast prions lacking these Gln/Asn-rich domains.
Purpose of the Study:
- To identify novel yeast prion proteins that do not contain Gln/Asn-rich domains.
- To characterize the prion-forming ability and functional consequences of a newly identified non-Gln/Asn-rich yeast prion.
Main Methods:
- Genome-wide screen using cross-seeding between heterologous proteins to find novel yeast prions.
- In vitro amyloid formation assays with the identified protein, Mod5.
- Introduction of Mod5 amyloids into non-prion yeast to assess prion induction and heritability.
- Analysis of [MOD (+)] yeast for ergosterol levels, antifungal resistance, and de novo prion formation under drug pressure.
Main Results:
- Mod5, a yeast tRNA isopentenyltransferase, was identified as a novel non-Gln/Asn-rich yeast prion protein.
- Mod5 formed self-propagating amyloid fibers in vitro.
- Introduction of Mod5 amyloids induced a dominant, cytoplasmically heritable prion state [MOD (+)] in yeast.
- [MOD (+)] yeast exhibited increased ergosterol levels and acquired resistance to antifungal agents.
- Antifungal drug pressure enhanced de novo formation of the [MOD (+)] prion state.
Conclusions:
- The study expands the known repertoire of yeast prions to include proteins lacking Gln/Asn-rich domains.
- The Mod5 prion confers a fitness advantage, enhancing cell survival under antifungal stress.
- Active prion conversion can lead to acquired traits beneficial for organismal survival.
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