Prion-Forming Ability of Ure2 of Yeasts Is Not Evolutionarily Conserved

Edskes, Herman K.; Engel, Abbi; McCann, Lindsay M.; Brachmann, Andreas; Tsai, Huei‐Fung; Wickner, Reed B.

doi:10.1534/genetics.111.127217

Cited by 29 publications

(53 citation statements)

References 78 publications

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“…Hsp104p dramatically promotes the prion conversion of Ure2p from C. albicans: We used the cerevisiae strain BY302 having the C. albicans URE2 open reading frame in place of that of cerevisiae, but driven by the cerevisiae URE2 promoter (Edskes et al 2011). Among the genes derepressed on inactivation of Ure2p by prion formation is DAL5, encoding the allantoate permease (Turoscy and Cooper 1987).…”

Section: Resultsmentioning

confidence: 99%

“…BY302 also carries ADE2 under control of the DAL5 promoter so that an active Ure2 alb gives red Ade 2 colonies and an inactive Ure2 alb results in white Ade 1 clones (Brachmann et al 2005). The C. albicans Ure2 protein (Ure2p alb ) can form the [URE3alb] prion in S. cerevisiae (Edskes et al 2011) and, as with other prions (Wickner 1994), the frequency of prion formation is dramatically increased when this protein is overexpressed (Edskes et al 2011 Figure S1). …”

Section: Resultsmentioning

confidence: 99%

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Molecular Chaperone Hsp104 Can Promote Yeast Prion Generation

et al. 2011

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ABSTRACT[URE3] is an amyloid-based prion of Ure2p, a regulator of nitrogen catabolism in Saccharomyces cerevisiae. The Ure2p of the human pathogen Candida albicans can also be a prion in S. cerevisiae. We find that overproduction of the disaggregating chaperone, Hsp104, increases the frequency of de novo [URE3] prion formation by the Ure2p of S. cerevisiae and that of C. albicans. This stimulation is strongly dependent on the presence of the [PIN 1 ] prion, known from previous work to enhance [URE3] prion generation. Our data suggest that transient Hsp104 overproduction enhances prion generation through persistent effects on Rnq1 amyloid, as well as during overproduction by disassembly of amorphous Ure2 aggregates (generated during Ure2p overproduction), driving the aggregation toward the amyloid pathway. Overproduction of other major cytosolic chaperones of the Hsp70 and Hsp40 families (Ssa1p, Sse1p, and Ydj1p) inhibit prion formation, whereas another yeast Hsp40, Sis1p, modulates the effects of Hsp104p on both prion induction and prion curing in a prion-specific manner. The same factor may both enhance de novo prion generation and destabilize existing prion variants, suggesting that prion variants may be selected by changes in the chaperone network.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Molecular Chaperone Hsp104 Can Promote Yeast Prion Generation

et al. 2011

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“…Extensive barriers to transmission of [PSI+] between wild S. cerevisiae have been found, suggesting that this protection from "catching" a prion has been selected in evolution (34). The notion that prion-forming ability is generally conserved (46) is not true for Ure2p, as the Saccharomyces castellii, Kluyveromyces lactis, and Candida glabrata Ure2ps cannot become [URE3] even though they are closely related to that of S. cerevisiae Ure2p, whereas the more distantly related Candida albicans Ure2p can form a prion (33,49,50). Prion-forming ability appears to be sporadic rather than conserved.…”

Section: Discussionmentioning

confidence: 99%

Sex, prions, and plasmids in yeast

Kelly

Shewmaker

Kryndushkin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Even deadly prions may be widespread in nature if they spread by infection faster than they kill off their hosts. The yeast prions [PSI+] and [URE3] (amyloids of Sup35p and Ure2p) were not found in 70 wild strains, while [PIN+] (amyloid of Rnq1p) was found in ∼16% of the same population. Yeast prion infection occurs only by mating, balancing the detrimental effects of carrying the prion. We estimated the frequency of outcross mating as about 1% of mitotic doublings from the known detriment of carrying the 2-μm DNA plasmid (∼1%) and its frequency in wild populations (38/70). We also estimated the fraction of total matings that are outcross matings (∼23-46%) from the fraction of heterozygosity at the highly polymorphic RNQ1 locus (∼46% [PIN+] of S. cerevisiae are parallel in-register β-sheet amyloids of Sup35p, Ure2p, and Rnq1p, respectively (7-10); the [Het-s] prion of P. anserina is a β-helical amyloid of the HET-s protein (11). Sup35p is a subunit of the translation termination factor (12, 13), Ure2p is a regulator of nitrogen catabolism (14), and Rnq1p has no known function (15).The mammalian prions are uniformly lethal but nonetheless are found in wild animals. For example, chronic wasting disease of deer and elk is found in ∼10% of wild deer in parts of Wyoming, Colorado, Illinois, and Wisconsin (16). Evidently, infectious spread outpaces the lethal effects on the animals. The [Het-s] prion of P. anserina is involved in heterokaryon incompatibility, a normal function of that species, and, as a result, ∼80% of wild strains with the appropriate chromosomal genotype carry the [Het-s] (20), a result confirmed by others (21) and which we interpreted as meaning that they are substantially detrimental. Nonetheless, others argue that these prions are beneficial, promoting survival by allowing cells to resist stress (22, 23), although the reported effects were not reproducible with the same strains (24). It is reported further that certain stress conditions increase the frequency of[PSI+] when assayed using a synthetic Sup35p with an elevated prion-forming tendency (25). Here we test these conditions for an effect on prion formation by the wild-type Sup35p.Our argument, that the rare occurrence of an infectious agent in nature implies pathologic effects on the host, relies on outcross mating being a fairly frequent event. Yeast prions spread only by mating (there is no extracellular prion species in the replication cycle), and if outcross mating is extremely rare, then yeast prions could be rare even if their effects on the host were neutral. Yeast spores germinate with mating type either a or α, and a and α spores from the same tetrad may mate (intratetrad or brothersister). The mating-type switching system (homothallism) results in the clone from a single germinated spore becoming a mixture of a and α cells which can mate with each other. These two kinds of "selfing" are unlikely to spread any virus, plasmid, or prion, because probably both mating partners will lack the element, or both will have it. Alternat...

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“…Indeed, while many (but not all) close or distant Sup35p and Ure2p orthologs have been shown to have prion forming abilities when expressed in Saccharomyces cerevisiae, evidence for such prion propagation in their natural hosts is rather scarce. [66][67][68][69][70][71][72][73] This may be due to unique properties (e.g., molecular chaperones, quality-control sub-cellular compartments, etc.,) evolved by S. cerevisiae laboratory strains that are required for the maintenance and propagation of prions. In a recent study, we showed for the first time that a single amino-acid change within the C-terminal domain of Sup35p dramatically affects its prion properties.…”

Section: The [Psi + ] and [Ure3] Prionsmentioning

confidence: 99%