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Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae
I L Derkatch1, Y O Chernoff, V V Kushnirov
1Department of Biological Sciences, University of Illinois at Chicago 60607, USA.
Abstract:
We have previously shown that multicopy plasmids containing the complete SUP35 gene are able to induce the appearance of the non-Mendelian factor [PSI]. This result was later interpreted by others as a crucial piece of evidence for a model postulating that [PSI] is a self-modified, prion-like conformational derivative of the Sup35 protein. Here we support this interpretation by proving that it is the overproduction of Sup35 protein, and not the excess of SUP35 DNA or mRNA that causes the appearance of [PSI]. We also show that the "prion-inducing domain" of Sup35p is in the N-terminal region, which, like the "prion-inducing domain" of another yeast prion, Ure2p, was previously shown to be distinct from the functional domain of the protein. This suggests that such a chimeric organization may be a common pattern of some prion elements. Finally, we find that [PSI] factors of different efficiencies and different mitotic stabilities are induced in the same yeast strain by overproduction of the identical Sup35 protein. We suggest that the different [PSI]-containing derivatives are analogous to the mysterious mammalian prion strains and result from different conformational variants of Sup35p.
Insights
Overproducing the Sup35 protein, not its DNA or mRNA, causes the yeast prion [PSI] to appear. Different conformational variants of Sup35 protein may explain varying prion efficiencies, similar to mammalian prion strains.
Area of Science:
- Molecular biology
- Yeast genetics
- Prion biology
Background:
- The non-Mendelian factor [PSI] in yeast is linked to the SUP35 gene.
- Previous work suggested [PSI] is a prion-like conformational variant of the Sup35 protein.
Purpose of the Study:
- To confirm that Sup35 protein overproduction induces [PSI].
- To identify the protein domain responsible for prion induction.
- To investigate the basis for different [PSI] variants.
Main Methods:
- Yeast strains with multicopy plasmids expressing SUP35.
- Analysis of protein, DNA, and mRNA levels.
- Characterization of [PSI] variants.
Main Results:
- Sup35 protein overproduction, not excess DNA or mRNA, induces [PSI].
- The N-terminal region of Sup35p acts as the prion-inducing domain.
- Different conformational variants of Sup35p lead to distinct [PSI] factors with varying efficiencies and stabilities.
Conclusions:
- Protein overproduction is key to yeast prion formation.
- A modular domain structure (prion-inducing vs. functional) may be common in prions.
- Yeast [PSI] variants may be analogous to mammalian prion strains, arising from protein conformational diversity.