pmc.ncbi.nlm.nih.gov

Genetic and Environmental Factors Affecting the De Novo Appearance of the [Psi(+)] Prion in Saccharomyces Cerevisiae

Abstract

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.

Full Text

The Full Text of this article is available as a PDF (5.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bessen R. A., Kocisko D. A., Raymond G. J., Nandan S., Lansbury P. T., Caughey B. Non-genetic propagation of strain-specific properties of scrapie prion protein. Nature. 1995 Jun 22;375(6533):698–700. doi: 10.1038/375698a0. [DOI] [PubMed] [Google Scholar]
  2. Bessen R. A., Marsh R. F. Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. J Virol. 1992 Apr;66(4):2096–2101. doi: 10.1128/jvi.66.4.2096-2101.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bonneaud N., Ozier-Kalogeropoulos O., Li G. Y., Labouesse M., Minvielle-Sebastia L., Lacroute F. A family of low and high copy replicative, integrative and single-stranded S. cerevisiae/E. coli shuttle vectors. Yeast. 1991 Aug-Sep;7(6):609–615. doi: 10.1002/yea.320070609. [DOI] [PubMed] [Google Scholar]
  4. Broach J. R., Hicks J. B. Replication and recombination functions associated with the yeast plasmid, 2 mu circle. Cell. 1980 Sep;21(2):501–508. doi: 10.1016/0092-8674(80)90487-0. [DOI] [PubMed] [Google Scholar]
  5. Bruce M. E., Fraser H. Scrapie strain variation and its implications. Curr Top Microbiol Immunol. 1991;172:125–138. doi: 10.1007/978-3-642-76540-7_8. [DOI] [PubMed] [Google Scholar]
  6. Büeler H., Aguzzi A., Sailer A., Greiner R. A., Autenried P., Aguet M., Weissmann C. Mice devoid of PrP are resistant to scrapie. Cell. 1993 Jul 2;73(7):1339–1347. doi: 10.1016/0092-8674(93)90360-3. [DOI] [PubMed] [Google Scholar]
  7. Caughey B., Chesebro B. Prion protein and the transmissible spongiform encephalopathies. Trends Cell Biol. 1997 Feb;7(2):56–62. doi: 10.1016/S0962-8924(96)10054-4. [DOI] [PubMed] [Google Scholar]
  8. Chernoff Y. O., Derkach I. L., Inge-Vechtomov S. G. Multicopy SUP35 gene induces de-novo appearance of psi-like factors in the yeast Saccharomyces cerevisiae. Curr Genet. 1993 Sep;24(3):268–270. doi: 10.1007/BF00351802. [DOI] [PubMed] [Google Scholar]
  9. Chernoff Y. O., Lindquist S. L., Ono B., Inge-Vechtomov S. G., Liebman S. W. Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science. 1995 May 12;268(5212):880–884. doi: 10.1126/science.7754373. [DOI] [PubMed] [Google Scholar]
  10. Cox B. S. A recessive lethal super-suppressor mutation in yeast and other psi phenomena. Heredity (Edinb) 1971 Apr;26(2):211–232. doi: 10.1038/hdy.1971.28. [DOI] [PubMed] [Google Scholar]
  11. Cox B. S., Tuite M. F., McLaughlin C. S. The psi factor of yeast: a problem in inheritance. Yeast. 1988 Sep;4(3):159–178. doi: 10.1002/yea.320040302. [DOI] [PubMed] [Google Scholar]
  12. Cox B. Cytoplasmic inheritance. Prion-like factors in yeast. Curr Biol. 1994 Aug 1;4(8):744–748. doi: 10.1016/s0960-9822(00)00167-6. [DOI] [PubMed] [Google Scholar]
  13. Dagkesamanskaya A. R., Ter-Avanesyan M. D. Interaction of the yeast omnipotent suppressors SUP1(SUP45) and SUP2(SUP35) with non-mendelian factors. Genetics. 1991 Jul;128(3):513–520. doi: 10.1093/genetics/128.3.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Derkatch I. L., Chernoff Y. O., Kushnirov V. V., Inge-Vechtomov S. G., Liebman S. W. Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. Genetics. 1996 Dec;144(4):1375–1386. doi: 10.1093/genetics/144.4.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dickinson A. G., Meikle V. M. Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Mol Gen Genet. 1971;112(1):73–79. doi: 10.1007/BF00266934. [DOI] [PubMed] [Google Scholar]
  16. Eustice D. C., Wakem L. P., Wilhelm J. M., Sherman F. Altered 40 S ribosomal subunits in omnipotent suppressors of yeast. J Mol Biol. 1986 Mar 20;188(2):207–214. doi: 10.1016/0022-2836(86)90305-0. [DOI] [PubMed] [Google Scholar]
  17. Hunter N., Cairns D., Foster J. D., Smith G., Goldmann W., Donnelly K. Is scrapie solely a genetic disease? Nature. 1997 Mar 13;386(6621):137–137. doi: 10.1038/386137a0. [DOI] [PubMed] [Google Scholar]
  18. Jensen R., Sprague G. F., Jr, Herskowitz I. Regulation of yeast mating-type interconversion: feedback control of HO gene expression by the mating-type locus. Proc Natl Acad Sci U S A. 1983 May;80(10):3035–3039. doi: 10.1073/pnas.80.10.3035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kaneko K., Vey M., Scott M., Pilkuhn S., Cohen F. E., Prusiner S. B. COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2333–2338. doi: 10.1073/pnas.94.6.2333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lindquist S., Kim G. Heat-shock protein 104 expression is sufficient for thermotolerance in yeast. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5301–5306. doi: 10.1073/pnas.93.11.5301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lindquist S., Patino M. M., Chernoff Y. O., Kowal A. S., Singer M. A., Liebman S. W., Lee K. H., Blake T. The role of Hsp104 in stress tolerance and [PSI+] propagation in Saccharomyces cerevisiae. Cold Spring Harb Symp Quant Biol. 1995;60:451–460. doi: 10.1101/sqb.1995.060.01.050. [DOI] [PubMed] [Google Scholar]
  22. Lund P. M., Cox B. S. Reversion analysis of [psi-] mutations in Saccharomyces cerevisiae. Genet Res. 1981 Apr;37(2):173–182. doi: 10.1017/s0016672300020140. [DOI] [PubMed] [Google Scholar]
  23. Masison D. C., Wickner R. B. Prion-inducing domain of yeast Ure2p and protease resistance of Ure2p in prion-containing cells. Science. 1995 Oct 6;270(5233):93–95. doi: 10.1126/science.270.5233.93. [DOI] [PubMed] [Google Scholar]
  24. Ono B., Ishino-Arao Y., Tanaka M., Awano I., Shinoda S. Recessive nonsense suppressors in Saccharomyces cerevisiae: action spectra, complementation groups and map positions. Genetics. 1986 Oct;114(2):363–374. doi: 10.1093/genetics/114.2.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Palmer E., Wilhelm J. M., Sherman F. Phenotypic suppression of nonsense mutants in yeast by aminoglycoside antibiotics. Nature. 1979 Jan 11;277(5692):148–150. doi: 10.1038/277148a0. [DOI] [PubMed] [Google Scholar]
  26. Parsell D. A., Kowal A. S., Singer M. A., Lindquist S. Protein disaggregation mediated by heat-shock protein Hsp104. Nature. 1994 Dec 1;372(6505):475–478. doi: 10.1038/372475a0. [DOI] [PubMed] [Google Scholar]
  27. Patino M. M., Liu J. J., Glover J. R., Lindquist S. Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science. 1996 Aug 2;273(5275):622–626. doi: 10.1126/science.273.5275.622. [DOI] [PubMed] [Google Scholar]
  28. Paushkin S. V., Kushnirov V. V., Smirnov V. N., Ter-Avanesyan M. D. 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] [Google Scholar]
  29. Prusiner S. B. Biology and genetics of prion diseases. Annu Rev Microbiol. 1994;48:655–686. doi: 10.1146/annurev.mi.48.100194.003255. [DOI] [PubMed] [Google Scholar]
  30. Prusiner S. B., Groth D., Serban A., Koehler R., Foster D., Torchia M., Burton D., Yang S. L., DeArmond S. J. Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10608–10612. doi: 10.1073/pnas.90.22.10608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Prusiner S. B. Molecular biology and pathogenesis of prion diseases. Trends Biochem Sci. 1996 Dec;21(12):482–487. doi: 10.1016/s0968-0004(96)10063-3. [DOI] [PubMed] [Google Scholar]
  32. Sanchez Y., Lindquist S. L. HSP104 required for induced thermotolerance. Science. 1990 Jun 1;248(4959):1112–1115. doi: 10.1126/science.2188365. [DOI] [PubMed] [Google Scholar]
  33. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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. doi: 10.1073/pnas.76.4.1952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Singh A., Ursic D., Davies J. Phenotypic suppression and misreading Saccharomyces cerevisiae. Nature. 1979 Jan 11;277(5692):146–148. doi: 10.1038/277146a0. [DOI] [PubMed] [Google Scholar]
  36. Stansfield I., Jones K. M., Kushnirov V. V., Dagkesamanskaya A. R., Poznyakovski A. I., Paushkin S. V., Nierras C. R., Cox B. S., Ter-Avanesyan M. D., Tuite M. F. 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. doi: 10.1002/j.1460-2075.1995.tb00111.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Struhl K., Stinchcomb D. T., Scherer S., Davis R. W. High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1035–1039. doi: 10.1073/pnas.76.3.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ter-Avanesyan M. D., Dagkesamanskaya A. R., Kushnirov V. V., Smirnov V. N. 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. doi: 10.1093/genetics/137.3.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ter-Avanesyan M. D., Kushnirov V. V., Dagkesamanskaya A. R., Didichenko S. A., Chernoff Y. O., Inge-Vechtomov S. G., Smirnov V. N. 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. doi: 10.1111/j.1365-2958.1993.tb01159.x. [DOI] [PubMed] [Google Scholar]
  40. Tuite M. F., Lindquist S. L. Maintenance and inheritance of yeast prions. Trends Genet. 1996 Nov;12(11):467–471. doi: 10.1016/0168-9525(96)10045-7. [DOI] [PubMed] [Google Scholar]
  41. Tuite M. F., Mundy C. R., Cox B. S. Agents that cause a high frequency of genetic change from [psi+] to [psi-] in Saccharomyces cerevisiae. Genetics. 1981 Aug;98(4):691–711. doi: 10.1093/genetics/98.4.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Weissmann C. The Ninth Datta Lecture. Molecular biology of transmissible spongiform encephalopathies. FEBS Lett. 1996 Jun 24;389(1):3–11. doi: 10.1016/0014-5793(96)00610-2. [DOI] [PubMed] [Google Scholar]
  43. Wickner R. B., Masison D. C., Edskes H. K. [PSI] and [URE3] as yeast prions. Yeast. 1995 Dec;11(16):1671–1685. doi: 10.1002/yea.320111609. [DOI] [PubMed] [Google Scholar]
  44. Wickner R. B. [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science. 1994 Apr 22;264(5158):566–569. doi: 10.1126/science.7909170. [DOI] [PubMed] [Google Scholar]
  45. 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. doi: 10.1002/j.1460-2075.1995.tb00078.x. [DOI] [PMC free article] [PubMed] [Google Scholar]