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EMBO J. Mar 1, 1999; 18(5): 1182–1191.
PMCID: PMC1171209

The yeast non-Mendelian factor [ETA+] is a variant of [PSI+], a prion-like form of release factor eRF3.

Abstract

The yeast non-Mendelian factor [ETA+] is lethal in the presence of certain mutations in the SUP35 and SUP45 genes, which code for the translational release factors eRF3 and eRF1, respectively. One such mutation, sup35-2, is now shown to contain a UAG stop codon prior to the essential region of the gene. The non-Mendelian inheritance of [ETA+] is reminiscent of the yeast [PSI+] element, which is due to a self-propagating conformation of Sup35p. Here we show that [ETA+] and [PSI+] share many characteristics. Indeed, like [PSI+], the maintenance of [ETA+] requires the N-terminal region of Sup35p and depends on an appropriate level of the chaperone protein Hsp104. Moreover, [ETA+] can be induced de novo by excess Sup35p, and [ETA+] cells have a weak nonsense suppressor phenotype characteristic of weak [PSI+]. We conclude that [ETA+] is actually a weak, unstable variant of [PSI+]. We find that although some Sup35p aggregates in [ETA+] cells, more Sup35p remains soluble in [ETA+] cells than in isogenic strong [PSI+] cells. Our data suggest that the amount of soluble Sup35p determines the strength of translational nonsense suppression associated with different [PSI+] variants.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aigle M, Lacroute F. Genetical aspects of [URE3], a non-mitochondrial, cytoplasmically inherited mutation in yeast. Mol Gen Genet. 1975;136(4):327–335. [PubMed]
  • Bonetti B, Fu L, Moon J, Bedwell DM. The efficiency of translation termination is determined by a synergistic interplay between upstream and downstream sequences in Saccharomyces cerevisiae. J Mol Biol. 1995 Aug 18;251(3):334–345. [PubMed]
  • Broach JR, Strathern JN, Hicks JB. Transformation in yeast: development of a hybrid cloning vector and isolation of the CAN1 gene. Gene. 1979 Dec;8(1):121–133. [PubMed]
  • Caughey B, Chesebro B. Prion protein and the transmissible spongiform encephalopathies. Trends Cell Biol. 1997 Feb;7(2):56–62. [PubMed]
  • Chernov Iu O, Derkach IL, Dagkesmanskaia AR, Tikhomirova VL, Ter-Avanesian MD. Nonsens-supressiia pri amplifikatsii gena, kodiruiushchego belkovyi faktor transliatsii. Dokl Akad Nauk SSSR. 1988;301(5):1227–1229. [PubMed]
  • Chernoff YO, Inge-Vechtomov SG, Derkach IL, Ptyushkina MV, Tarunina OV, Dagkesamanskaya AR, Ter-Avanesyan MD. Dosage-dependent translational suppression in yeast Saccharomyces cerevisiae. Yeast. 1992 Jul;8(7):489–499. [PubMed]
  • Chernoff YO, Derkach IL, Inge-Vechtomov SG. Multicopy SUP35 gene induces de-novo appearance of psi-like factors in the yeast Saccharomyces cerevisiae. Curr Genet. 1993 Sep;24(3):268–270. [PubMed]
  • Chernoff YO, Lindquist SL, Ono B, Inge-Vechtomov SG, Liebman SW. Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science. 1995 May 12;268(5212):880–884. [PubMed]
  • Cohen FE, Pan KM, Huang Z, Baldwin M, Fletterick RJ, Prusiner SB. Structural clues to prion replication. Science. 1994 Apr 22;264(5158):530–531. [PubMed]
  • Cox BS. A recessive lethal super-suppressor mutation in yeast and other psi phenomena. Heredity (Edinb) 1971 Apr;26(2):211–232. [PubMed]
  • Cox BS, Tuite MF, McLaughlin CS. The psi factor of yeast: a problem in inheritance. Yeast. 1988 Sep;4(3):159–178. [PubMed]
  • Crouzet M, Tuite MF. Genetic control of translational fidelity in yeast: molecular cloning and analysis of the allosuppressor gene SAL3. Mol Gen Genet. 1987 Dec;210(3):581–583. [PubMed]
  • Crouzet M, Izgu F, Grant CM, Tuite MF. The allosuppressor gene SAL4 encodes a protein important for maintaining translational fidelity in Saccharomyces cerevisiae. Curr Genet. 1988 Dec;14(6):537–543. [PubMed]
  • Czaplinski K, Ruiz-Echevarria MJ, Paushkin SV, Han X, Weng Y, Perlick HA, Dietz HC, Ter-Avanesyan MD, Peltz SW. The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs. Genes Dev. 1998 Jun 1;12(11):1665–1677. [PMC free article] [PubMed]
  • Dagkesamanskaya AR, Ter-Avanesyan MD. Interaction of the yeast omnipotent suppressors SUP1(SUP45) and SUP2(SUP35) with non-mendelian factors. Genetics. 1991 Jul;128(3):513–520. [PMC free article] [PubMed]
  • Derkatch IL, Chernoff YO, Kushnirov VV, Inge-Vechtomov SG, Liebman SW. Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. Genetics. 1996 Dec;144(4):1375–1386. [PMC free article] [PubMed]
  • Derkatch IL, Bradley ME, Zhou P, Chernoff YO, Liebman SW. Genetic and environmental factors affecting the de novo appearance of the [PSI+] prion in Saccharomyces cerevisiae. Genetics. 1997 Oct;147(2):507–519. [PMC free article] [PubMed]
  • Derkatch IL, Bradley ME, Liebman SW. Overexpression of the SUP45 gene encoding a Sup35p-binding protein inhibits the induction of the de novo appearance of the [PSI+] prion. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2400–2405. [PMC free article] [PubMed]
  • Doel SM, McCready SJ, Nierras CR, Cox BS. The dominant PNM2- mutation which eliminates the psi factor of Saccharomyces cerevisiae is the result of a missense mutation in the SUP35 gene. Genetics. 1994 Jul;137(3):659–670. [PMC free article] [PubMed]
  • Drugeon G, Jean-Jean O, Frolova L, Le Goff X, Philippe M, Kisselev L, Haenni AL. Eukaryotic release factor 1 (eRF1) abolishes readthrough and competes with suppressor tRNAs at all three termination codons in messenger RNA. Nucleic Acids Res. 1997 Jun 15;25(12):2254–2258. [PMC free article] [PubMed]
  • Frolova L, Le Goff X, Rasmussen HH, Cheperegin S, Drugeon G, Kress M, Arman I, Haenni AL, Celis JE, Philippe M, et al. A highly conserved eukaryotic protein family possessing properties of polypeptide chain release factor. Nature. 1994 Dec 15;372(6507):701–703. [PubMed]
  • Glover JR, Kowal AS, Schirmer EC, Patino MM, Liu JJ, Lindquist S. Self-seeded fibers formed by Sup35, the protein determinant of [PSI+], a heritable prion-like factor of S. cerevisiae. Cell. 1997 May 30;89(5):811–819. [PubMed]
  • Griffith JS. Self-replication and scrapie. Nature. 1967 Sep 2;215(5105):1043–1044. [PubMed]
  • Hoffman CS, Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. [PubMed]
  • Ito H, Fukuda Y, Murata K, Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. [PMC free article] [PubMed]
  • Jarrett JT, Lansbury PT., Jr Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell. 1993 Jun 18;73(6):1055–1058. [PubMed]
  • King CY, Tittmann P, Gross H, Gebert R, Aebi M, Wüthrich K. Prion-inducing domain 2-114 of yeast Sup35 protein transforms in vitro into amyloid-like filaments. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6618–6622. [PMC free article] [PubMed]
  • Kochneva-Pervukhova NV, Poznyakovski AI, Smirnov VN, Ter-Avanesyan MD. C-terminal truncation of the Sup35 protein increases the frequency of de novo generation of a prion-based [PSI+] determinant in Saccharomyces cerevisiae. Curr Genet. 1998 Aug;34(2):146–151. [PubMed]
  • Kushnirov VV, Ter-Avanesyan MD, Telckov MV, Surguchov AP, Smirnov VN, Inge-Vechtomov SG. Nucleotide sequence of the SUP2 (SUP35) gene of Saccharomyces cerevisiae. Gene. 1988 Jun 15;66(1):45–54. [PubMed]
  • Le Goff X, Philippe M, Jean-Jean O. Overexpression of human release factor 1 alone has an antisuppressor effect in human cells. Mol Cell Biol. 1997 Jun;17(6):3164–3172. [PMC free article] [PubMed]
  • Liebman SW, Cavenagh M. An antisuppressor that acts on omnipotent suppressors in yeast. Genetics. 1980 May;95(1):49–61. [PMC free article] [PubMed]
  • Liebman SW, Derkatch IL. The yeast [PSI+] prion: making sense of nonsense. J Biol Chem. 1999 Jan 15;274(3):1181–1184. [PubMed]
  • Mottagui-Tabar S, Tuite MF, Isaksson LA. The influence of 5' codon context on translation termination in Saccharomyces cerevisiae. Eur J Biochem. 1998 Oct 1;257(1):249–254. [PubMed]
  • Patino MM, Liu JJ, Glover JR, Lindquist S. Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science. 1996 Aug 2;273(5275):622–626. [PubMed]
  • Paushkin SV, Kushnirov VV, Smirnov VN, Ter-Avanesyan MD. Propagation of the yeast prion-like [psi+] determinant is mediated by oligomerization of the SUP35-encoded polypeptide chain release factor. EMBO J. 1996 Jun 17;15(12):3127–3134. [PMC free article] [PubMed]
  • Paushkin SV, Kushnirov VV, Smirnov VN, Ter-Avanesyan MD. In vitro propagation of the prion-like state of yeast Sup35 protein. Science. 1997 Jul 18;277(5324):381–383. [PubMed]
  • Paushkin SV, Kushnirov VV, Smirnov VN, Ter-Avanesyan MD. Interaction between yeast Sup45p (eRF1) and Sup35p (eRF3) polypeptide chain release factors: implications for prion-dependent regulation. Mol Cell Biol. 1997 May;17(5):2798–2805. [PMC free article] [PubMed]
  • Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982 Apr 9;216(4542):136–144. [PubMed]
  • Prusiner SB. Molecular biology and pathogenesis of prion diseases. Trends Biochem Sci. 1996 Dec;21(12):482–487. [PubMed]
  • Rose MD, Novick P, Thomas JH, Botstein D, Fink GR. A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. Gene. 1987;60(2-3):237–243. [PubMed]
  • Rothstein RJ. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Singh A, Helms C, Sherman F. Mutation of the non-Mendelian suppressor, Psi, in yeast by hypertonic media. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1952–1956. [PMC free article] [PubMed]
  • Song JM, Liebman SW. Interaction of UAG suppressors and omnipotent suppressors in Saccharomyces cerevisiae. J Bacteriol. 1985 Feb;161(2):778–780. [PMC free article] [PubMed]
  • Stansfield I, Jones KM, Kushnirov VV, Dagkesamanskaya AR, Poznyakovski AI, Paushkin SV, Nierras CR, Cox BS, Ter-Avanesyan MD, Tuite MF. The products of the SUP45 (eRF1) and SUP35 genes interact to mediate translation termination in Saccharomyces cerevisiae. EMBO J. 1995 Sep 1;14(17):4365–4373. [PMC free article] [PubMed]
  • Ter-Avanesyan MD, Kushnirov VV, Dagkesamanskaya AR, Didichenko SA, Chernoff YO, Inge-Vechtomov SG, Smirnov VN. Deletion analysis of the SUP35 gene of the yeast Saccharomyces cerevisiae reveals two non-overlapping functional regions in the encoded protein. Mol Microbiol. 1993 Mar;7(5):683–692. [PubMed]
  • Ter-Avanesyan MD, Dagkesamanskaya AR, Kushnirov VV, Smirnov VN. The SUP35 omnipotent suppressor gene is involved in the maintenance of the non-Mendelian determinant [psi+] in the yeast Saccharomyces cerevisiae. Genetics. 1994 Jul;137(3):671–676. [PMC free article] [PubMed]
  • Tuite MF, Mundy CR, Cox BS. Agents that cause a high frequency of genetic change from [psi+] to [psi-] in Saccharomyces cerevisiae. Genetics. 1981 Aug;98(4):691–711. [PMC free article] [PubMed]
  • Weissmann C. Molecular genetics of transmissible spongiform encephalopathies. J Biol Chem. 1999 Jan 1;274(1):3–6. [PubMed]
  • Wickner RB. [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science. 1994 Apr 22;264(5158):566–569. [PubMed]
  • Wilson PG, Culbertson MR. SUF12 suppressor protein of yeast. A fusion protein related to the EF-1 family of elongation factors. J Mol Biol. 1988 Feb 20;199(4):559–573. [PubMed]
  • Zhouravleva G, Frolova L, Le Goff X, Le Guellec R, Inge-Vechtomov S, Kisselev L, Philippe M. Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRF1 and eRF3. EMBO J. 1995 Aug 15;14(16):4065–4072. [PMC free article] [PubMed]

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