Genesis and Variability of [PSI] Prion Factors in Saccharomyces cerevisiae

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.

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Prion Variants of Yeast are Numerous, Mutable, and Segregate on Growth, Affecting Prion Pathogenesis, Transmission Barriers, and Sensitivity to Anti-Prion Systems

Viruses ◽

10.3390/v11030238 ◽

2019 ◽

Vol 11 (3) ◽

pp. 238 ◽

Cited By ~ 7

Author(s):

Reed Wickner ◽

Moonil Son ◽

Herman Edskes

Keyword(s):

Saccharomyces Cerevisiae ◽

Protein Sequence ◽

Biological Properties ◽

Yeast Prion ◽

Factors Affecting ◽

Prion Strains ◽

Immune Deficiencies ◽

Wild Strains ◽

Β Sheet ◽

Selective Effects

The known amyloid-based prions of Saccharomyces cerevisiae each have multiple heritable forms, called “prion variants” or “prion strains”. These variants, all based on the same prion protein sequence, differ in their biological properties and their detailed amyloid structures, although each of the few examined to date have an in-register parallel folded β sheet architecture. Here, we review the range of biological properties of yeast prion variants, factors affecting their generation and propagation, the interaction of prion variants with each other, the mutability of prions, and their segregation during mitotic growth. After early differentiation between strong and weak stable and unstable variants, the parameters distinguishing the variants has dramatically increased, only occasionally correlating with the strong/weak paradigm. A sensitivity to inter- and intraspecies barriers, anti-prion systems, and chaperone deficiencies or excesses and other factors all have dramatic selective effects on prion variants. Recent studies of anti-prion systems, which cure prions in wild strains, have revealed an enormous array of new variants, normally eliminated as they arise and so not previously studied. This work suggests that defects in the anti-prion systems, analogous to immune deficiencies, may be at the root of some human amyloidoses.

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The SUP35 omnipotent suppressor gene is involved in the maintenance of the non-Mendelian determinant [psi+] in the yeast Saccharomyces cerevisiae.

Genetics ◽

10.1093/genetics/137.3.671 ◽

1994 ◽

Vol 137 (3) ◽

pp. 671-676 ◽

Cited By ~ 23

Author(s):

M D Ter-Avanesyan ◽

A R Dagkesamanskaya ◽

V V Kushnirov ◽

V N Smirnov

Keyword(s):

Saccharomyces Cerevisiae ◽

Elongation Factor ◽

Suppressor Gene ◽

Terminal Region ◽

Recessive Trait ◽

Yeast Saccharomyces Cerevisiae ◽

Haploid Strain ◽

Suppressor Effect ◽

Sup35 Gene

Abstract The SUP35 gene of yeast Saccharomyces cerevisiae encodes a 76.5-kD ribosome-associated protein (Sup35p), the C-terminal part of which exhibits a high degree of similarity to EF-1 alpha elongation factor, while its N-terminal region is unique. Mutations in or overexpression of the SUP35 gene can generate an omnipotent suppressor effect. In the present study the SUP35 wild-type gene was replaced with deletion alleles generated in vitro that encode Sup35p lacking all or a part of the unique N-terminal region. These 5'-deletion alleles lead, in a haploid strain, simultaneously to an antisuppressor effect and to loss of the non-Mendelian determinant [psi+]. The antisuppressor effect is dominant while the elimination of the [psi+] determinant is a recessive trait. A set of the plasmid-borne deletion alleles of the SUP35 gene was tested for the ability to maintain [psi+]. It was shown that the first 114 amino acids of Sup35p are sufficient to maintain the [psi+] determinant. We propose that the Sup35p serves as a trans-acting factor required for the maintenance of [psi+].

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Genetic and Environmental Factors Affecting the de novo Appearance of the [PSI + ] Prion in Saccharomyces cerevisiae

Genetics ◽

10.1093/genetics/147.2.507 ◽

1997 ◽

Vol 147 (2) ◽

pp. 507-519 ◽

Cited By ~ 33

Author(s):

Irina L Derkatch ◽

Michael E Bradley ◽

Ping Zhou ◽

Yury O Chernoff ◽

Susan W Liebman

Keyword(s):

De Novo ◽

Proximal Part ◽

Yeast Prion ◽

Factors Affecting ◽

Yeast Strains ◽

N Terminus ◽

Mendelian Factor ◽

Conformational Determinant ◽

Genetic And Environmental Factors ◽

Sup35 Gene

It has previously been shown that yeast prion [PSI + ] is cured by GuHCl, although reports on reversibility of curing were contradictory. Here we show that GuHCl treatment of both [PSI + ] and [psi – ] yeast strains results in two classes of [psi – ] derivatives: Pin+, in which [PSI + ] can be reinduced by Sup35p overproduction, and Pin–, in which overexpression of the complete SUP35 gene does not lead to the [PSI + ] appearance. However, in both Pin+ and Pin– derivatives [PSI + ] is reinduced by overproduction of a short Sup35p N-terminal fragment, thus, in principle, [PSI + ] curing remains reversible in both cases. Neither suppression nor growth inhibition caused by SUP35 overexpression in Pin+ [psi – ] derivatives are observed in Pin– [psi – ] derivatives. Genetic analyses show that the Pin+ phenotype is determined by a non-Mendelian factor, which, unlike the [PSI + ] prion, is independent of the Sup35p N-terminal domain. A Pin– [psi – ] derivative was also generated by transient inactivation of the heat shock protein, Hsp104, while [PSI + ] curing by Hsp104 overproduction resulted exclusively in Pin+ [psi – ] derivatives. We hypothesize that in addition to the [PSI + ] prion-determining domain in the Sup35p N-terminus, there is another self-propagating conformational determinant in the C-proximal part of Sup35p and that this second prion is responsible for the Pin+ phenotype.

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Isolation of omnipotent suppressors in an [eta+] yeast strain.

Genetics ◽

10.1093/genetics/124.3.505 ◽

1990 ◽

Vol 124 (3) ◽

pp. 505-514 ◽

Cited By ~ 1

Author(s):

J A All-Robyn ◽

D Kelley-Geraghty ◽

E Griffin ◽

N Brown ◽

S W Liebman

Keyword(s):

Yeast Strain ◽

Guanidine Hydrochloride ◽

Wild Type ◽

Translational Fidelity ◽

Genetic Analyses ◽

Mendelian Factor ◽

Nonsense Codons

Abstract Omnipotent suppressors decrease translational fidelity and cause misreading of nonsense codons. In the presence of the non-Mendelian factor [eta+], some alleles of previously isolated omnipotent suppressors are lethal. Thus the current search was conducted in an [eta+] strain in an effort to identify new suppressor loci. A new omnipotent suppressor, SUP39, and alleles of sup35, sup45, SUP44 and SUP46 were identified. Efficiencies of the dominant suppressors were dramatically reduced in strains that were cured of non-Mendelian factors by growth on guanidine hydrochloride. Wild-type alleles of SUP44 and SUP46 were cloned and these clones were used to facilitate the genetic analyses. SUP44 was shown to be on chromosome VII linked to cyh2, and SUP46 was clearly identified as distinct from the linked sup45.

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Identification of a Functional Domain Within the Essential Core of Histone H3 That Is Required for Telomeric and HM Silencing in Saccharomyces cerevisiae

Genetics ◽

10.1093/genetics/163.1.447 ◽

2003 ◽

Vol 163 (1) ◽

pp. 447-452 ◽

Cited By ~ 1

Author(s):

Jeffrey S Thompson ◽

Marilyn L Snow ◽

Summer Giles ◽

Leslie E McPherson ◽

Michael Grunstein

Keyword(s):

Saccharomyces Cerevisiae ◽

Amino Acid ◽

Amino Acid Substitution ◽

Histone H3 ◽

Single Amino Acid ◽

Functional Domain ◽

Partial Loss ◽

Histone Fold ◽

Gal1 Promoter ◽

Substitution Mutations

Abstract Fourteen novel single-amino-acid substitution mutations in histone H3 that disrupt telomeric silencing in Saccharomyces cerevisiae were identified, 10 of which are clustered within the α1 helix and L1 loop of the essential histone fold. Several of these mutations cause derepression of silent mating locus HML, and an additional subset cause partial loss of basal repression at the GAL1 promoter. Our results identify a new domain within the essential core of histone H3 that is required for heterochromatin-mediated silencing.

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The Crystal Structure of the N-terminal Region of the Alpha Subunit of Translation Initiation Factor 2 (eIF2α) from Saccharomyces cerevisiae Provides a View of the Loop Containing Serine 51, the Target of the eIF2α-specific Kinases

Journal of Molecular Biology ◽

10.1016/j.jmb.2003.09.045 ◽

2003 ◽

Vol 334 (2) ◽

pp. 187-195 ◽

Cited By ~ 33

Author(s):

Simrit Dhaliwal ◽

David W. Hoffman

Keyword(s):

Crystal Structure ◽

Saccharomyces Cerevisiae ◽

Translation Initiation ◽

Terminal Region ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Alpha Subunit ◽

Initiation Factor 2 ◽

Translation Initiation Factor 2

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Mutation in genes coding for glucose-induced degradation-deficient protein contribute to high malate production in yeast strains No. 28 and No. 77 used for industrial brewing of sake

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab031 ◽

2021 ◽

Author(s):

Hiroaki Negoro ◽

Atsushi Kotaka ◽

Hiroki Ishida

Keyword(s):

Saccharomyces Cerevisiae ◽

Organic Acids ◽

Nonsense Mutation ◽

Yeast Strain ◽

Homozygous Mutation ◽

Alcohol Fermentation ◽

Protein Coding ◽

Protein Coding Genes ◽

Yeast Strains

ABSTRACT Saccharomyces cerevisiae produces organic acids including malate during alcohol fermentation. Since malate contributes to the pleasant flavor of sake, high-malate-producing yeast strain No. 28 and No. 77 have been developed by the Brewing Society of Japan. In this study, the genes responsible for the high malate phenotype in these strains were investigated. We had found previously that the deletion of components of the glucose induced degradation-deficient (GID) complex led to high malate production in yeast. Upon examining GID protein-coding genes in yeast strain No. 28 and No. 77, a nonsense homozygous mutation of GID4 in strain No. 28, and of GID2 in strain No. 77, were identified as the cause of high malate production. Furthermore, complementary tests of these mutations indicated that the heterozygous nonsense mutation in GID2 was recessive. In contrast, the heterozygous nonsense mutation in GID4 was considered semi-dominant.

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