Skip to main content
SpringerLink
Log in

Polypeptide chain termination in Saccharomyces cerevisiae

  • Review
  • Published:
Current Genetics Aims and scope Submit manuscript

Summary

The study of translational termination in yeast has been approached largely through the identification of a range of mutations which either increase or decrease the efficiency of stop-codon recognition. Subsequent cloning of the genes encoding these factors has identified a number of proteins important for maintaining the fidelity of termination, including at least three ribosomal proteins (S5, S13, S28). Other non-ribosomal proteins have been identified by mutations which produce gross termination-accuracy defects, namely the SUP35 and SUP45 gene products which have closely-related higher eukaryote homologues (GST1-h and SUP45-h respectively) and which can complement the corresponding defective yeast proteins, implying that the yeast ribosome may be a good model for the termination apparatus existing in higher translation systems.

While the yeast mitochondrial release factor has been cloned (Pel et al. 1992), the corresponding cytosolic RF has not yet been identified. It seems likely, however, that the identification of the gene encoding eRF could be achieved using a multicopy antisuppressor screen such as that employed to clone the E. coli prfA gene (Weiss et al. 1984). Identification of the yeast eRF and an investigation of its interaction with other components of the yeast translational machinery will no doubt further the definition of the translational termination process.

While a large number of mutations have been isolated in which the efficiency of termination-codon recognition is impaired, it seems probable that a proportion of mutations within this class will comprise those where the accuracy of ‘A’ site codon-anticodon interaction is compromised: such defects would also have an effect on termination-codon suppression, allowing mis- or non-cognate tRNAs to bind stop-condons, causing nonsense suppression. The remainder of mutatoons affecting termination fidelity should represent mutations in genes coding for components of the termination apparatus, including the eRF: these mutations reduce the efficiency of termination, allowing nonsense suppression by low-efficiency natural suppressor tRNAs. Elucidation of the mechanism of termination in yeast will require discrimination between these two classes of mutations, thus allowing definition of termination-specific gene products.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abastado J-P, Miller PF, Jackson BM, Hinnebusch AG (1991) Suppression of ribosomal reinitiation at upstream open reading frames in amino-acid-starved cells forms the basis for GCN4 translational control. Mol Cell Biol 11:486–496

    Google Scholar 

  • Alksne LE, Warner JR (1993) A novel cloning strategy reveals the gene for the yeast homologue to Escherichia coli ribosomal protein S12. J Biol Chem 268:10813–10819

    Google Scholar 

  • Alksne LE, Anthony RA, Liebman SW, Warner JR (1993) An accuracy centre in the ribosome conserved over 2 billion years. Proc Natl Acad Sci USA 90:9538–9541

    Google Scholar 

  • Allen NP, Noller HF (1989) Mutations in ribosomal proteins S4 and S12 influence the higher-order structure of 16S ribosomal RNA. J Mol Biol 208:457–468

    Google Scholar 

  • All-Robyn JA, Brown N, Otaka E, Liebman SW (1990a) Sequence and functional similarity between a yeast ribosomal protein and the Escherichia coli S5 ram protein. Mol Cell Biol 10:6544–6553

    Google Scholar 

  • All-Robyn JA, Kelley-Geraghty D, Griffin E, Brown N, Liebman SW (1990b) Isolation of omnipotent suppressors in an [eta +] yeast strain. Genetics 124:505–514

    Google Scholar 

  • Breining P, Piepersberg W (1986) Yeast omnipotent suppressors SUP1 (SUP45): nucleotide sequence of the wild-type and a mutant gene. Nucleic Acids Res 14:5187–5197

    Google Scholar 

  • Breining P, Surguchov AP, Piepersberg W (1984) Cloning and identification of a DNA fragment coding for the SUP1 gene of Sacchromyces cerevisiae. Curr Genet 8:467–470

    Google Scholar 

  • Brown CM, Stockwell PA, Trotman CNA, Tate WP (1990) Sequence analysis suggests that tetranucleotides signal the termination of protein synthesis in eukaryotes. Nucleic Acids Res 18:6339–6345

    Google Scholar 

  • Capel MS, Engelman DM, Freeborn Br, Kjeldguard M, Langer JA, Ramakrishnan V, Schmidt DG, Scheider DK, Schoenborn BP, Siller LY, Yabuki S, Moore PB (1987) A complete mapping of the proteins in the small ribosomal subunit of Escherichia coli. Science 238:1403–1406

    Google Scholar 

  • Caskey CT (1980) Peptide chain termination. Trends Biochem Sci 5:234–237

    Google Scholar 

  • Caskey CT, Forrester WC, Tate WP, Ward CD (1984) Cloning of the Escherichia coli release factor 2 gene. J Bacteriol 158:365–368

    Google Scholar 

  • Chernoff YO, Derkatch IL, Dagkesamanskaya AR, Tikhomoriva VL Ter-Avnesyan MD, Inge-Vechtomov SG (1988) Nonsense suppression caused by the amplification of translation factor gene. Dokl Akad Nauk SSSR (Proc USSR Acad Sci, in Russian) 301:1227–1229

    Google Scholar 

  • Cox BS (1965) [psi], a cytoplasmic suppressor of super suppressor in yeast. Heredity 20:505–521

    Google Scholar 

  • Cox BS (1977) Allosuppressors in yeast. Genet Res 30:187–205

    Google Scholar 

  • Cox BS, Tuite MF, McLaughlin CS (1988) The [psi] factor of yeast: a problem in inheritance. Yeast 4:159–178

    Google Scholar 

  • Crouzet M, Tuite MF (1987) Genetic control of translational fidelity in yeast: molecular cloning and analysis of the allosuppressor gene SAL3. Mol Gen Genet 210:581–583

    Google Scholar 

  • Crouzet M, Izgu F, Grant CM, Tuite MF (1988) The allosuppressor gene SAL4 encodes a protein important for maintaining translational fidelity in Saccharomyces cerevisiae. Curr Genet 14:537–543

    Google Scholar 

  • Didichenko SA, Ter-Avanesyan MD, Smirnov VN (1991) Ribosome-bound EF-1α-like protein of yeast Saccharomyces cerevisiae. Eur J Biochem 198:705–711

    Google Scholar 

  • Doel SM, McCready SJ, Nierras CR, Cox BS (1993) The dominant PNM2 mutation which eliminates the [psi] factor of Saccharomyces cerevisiae is the result of a missense mutation in the SUP35 gene. Genetics (in press)

  • Eustice DC, Wakem LP, Wilhelm JM, Sherman F (1986) Altered 40 S ribosomal subunits in omnipotent suppressors of yeast. J Mol Biol 188:207–214

    Google Scholar 

  • Frovola LY, Fleckner J, Justessen J, Timms KM, Tate WP, Kisselev LL, Haenni A-L (1993a) Are the tryptophanyl-tRNA synthetase and the peptide chain release factor from higher eukaryotes one and the same protein? Eur J Biochem 212:457–466

    Google Scholar 

  • Frovola LY, Dalphin ME, Justesen J, Powell RJ, Drugeon G, McCaughan KK, Kisselev LL, Tate WP, Haenni A-L (1993b) Mammalian polypeptide chain release factor and tryptophanyl synthetase are distinct proteins. EMBO J 12:4013–4019

    Google Scholar 

  • Gefter ML, Russel RL (1969) Rote of modifications in tyrosine transfer RNA; a modified base affecting ribosome binding. J Mol Biol 39:145–157

    Google Scholar 

  • Gelugne J-P, Bell JB (1988) Modifiers of ochre suppressors in Saccharomyces cerevisiae that exhibit ochre suppressor-dependent amber suppression. Curr Genet 14:345–354

    Google Scholar 

  • Gerlach W (1975) Genetic properties of some amber-ochre super-suppressors in Saccharomyces cerevisiae. Mol Gen Genet 138:53–63

    Google Scholar 

  • Goldstein JL, Beaudet AL, Caskey CT (1970) Peptide termination with mammalian release factor. Proc Natl Acad Sci USA 67:99–106

    Google Scholar 

  • Grant CM (1990) Control of translational accuracy in yeast. PhD thesis, University of Kent at Canterbury

  • Grennet HE, Bounelis P, Fuller GM (1992) Identification of a human cDNA clone with high homology to yeast omnipotent suppressor 45. Gene 110:239–243

    Google Scholar 

  • Hawthorne DC, Leupold U (1974) Suppressor mutations in yeast. Curr Top Microbiol Immunol 64:1–47

    Google Scholar 

  • Himmelfarb HJ, Maicas E, Friesen JD (1985) Isolation of the SUP45 omnipotent suppressor gene of Saccharomyces cerevisiae and characterisation of its gene product. Mol Cell Biol 5:816–822

    Google Scholar 

  • Hinnebusch AG (1990) Involvement of an initiation factor and protein phosphorylation in translational control of GCN4 mRNA. Trends Biochem Sci 15:148–152

    Google Scholar 

  • Hirashima A, Kaji A (1972) Factor-dependent release of ribosomes from messenger RNA. J Mol Biol 65:43–58

    Google Scholar 

  • Hoshino S, Miyazawa H, Enomoto H, Hanaoka F, Kikuchi Y, Kikuchi AUM (1989) A human homologue of the yeast GST1 gene codes for a GTP binding protein and is expressed in a proliferation-dependent manner in mammalian cells. EMBO J 8:3807–3814

    Google Scholar 

  • Inge-Vechtomov SG, Andrianova VM (1970) Recessive super-suppressor in yeast. Genetika 6:103–115

    Google Scholar 

  • Ishiguro J (1981) Genetic and biochemical characterisation of anti-suppressor mutants in the yeast Saccharomyces cerevisiae. Curr Genet 4:197–204

    Google Scholar 

  • Ishiguro J, Ono B-I, Masurekar M, McLaughlin CS, Sherman F (1981) Altered ribosomal protein S11 from SUP46 suppressor of yeast. J Mol Biol 147:391–397

    Google Scholar 

  • Ito H, Wittman HG (1973) Amino-acid replacements S5 and S12 of two Escherichia coli revertants from streptomycin dependence to independence. Mol Gen Genet 127:19–32

    Google Scholar 

  • Kikuchi Y, Shimatake H, Kikuchi A (1988) A yeast gene required for the G1-to-S transition encodes a protein containing an A-kinase target site and a GTPase domain. EMBO J 7:1175–1185

    Google Scholar 

  • Klein HA, Capecchi MR (1971) Polypeptide chain termination. J Biol Chem 246:1055–1061

    Google Scholar 

  • Konecki DS, Aune KC, Tate W, Caskey CT (1977) Characterisation of reticulocyte release factor. J Biol Chem 252:4514–4520

    Google Scholar 

  • Kushnirov KK, Ter-Avenesyan MD, Surguchov AP, Smirnov VN, Inge-Vechtomov SG (1987) Localisation of possible functional domains of sup2 gene product of yeast Saccharomyces cerevisiae. FEBS Lett 215:257–260

    Google Scholar 

  • Kushnirov KK, Ter-Avenesyan MD, Telckov MV, Surguchov AP, Smirnov VN, Inge-Vechtomov SG (1988) Nucleotide sequence of the SUP2 (SUP35) gene of Saccharomyces cerevisiae. Gene 66:45–54

    Google Scholar 

  • Labouesse M (1990) The yeast mitochondrial leucyl-tRNA synthetase is a splicing factor for the excision of several group-I introns. Mol Gen Genet 224:209–221

    Google Scholar 

  • Laten H, Gorman J, Bock RM (1978) Isopentyladenosine-deficient tRNA from an antisuppressor mutant of Saccharomyces cerevisiae. Nucleic Acids Res 5:4329–4342

    Google Scholar 

  • Lee CC, Craigen WJ, Muzny DM, Harlow E, Caskey CT (1990) Cloning and expression of a mammalian peptide chain release factor with sequence similarity to tryptophanyl-tRNA synthetases. Proc Natl Acad Sci USA 87:3508–3512

    Google Scholar 

  • Liebman SW, All-Robyn JA (1984) A non-Mendelian factor [eta] causes lethality of yeast omnipotent suppressor strains. Curr Genet 8:567–573

    Google Scholar 

  • Liebman SW, Cavenagh M (1980) An antisuppressor that acts on omnipotent suppressors in yeast. Genetics 95:49–61

    Google Scholar 

  • Liebman SW, Cavenagh MM (1981) 40S ribosomal protein from a Saccharomyces cerevisiae antisuppressor mutant exhibiting a unique 2D gel pattern. Curr Genet 3:27–29

    Google Scholar 

  • Liebman SW, Cavenagh MM, Bennet LN (1980) Isolation and properties of an antisuppressor in Saccharomyces cerevisiae specific for an omnipotent suppressor. J Bacteriol 143:1527–1529

    Google Scholar 

  • Liebman SW, Vincent A, Song JM, All-Robyn J (1993) Mutations affecting translational accuracy in yeast. In: Brown AJP, Tuite MF, McCarthy JEG (eds) Protein synthesis and targeting in yeast. NATO ASI series. Springer, New York Berlin Heidelberg, pp 91–100

    Google Scholar 

  • Linder P (1992) Molecular biology of translation in yeast. Ant von Leeuwenhoeck 62:47–62

    Google Scholar 

  • Macino G, Coruzzi G, Nobrega FG, Li M, Tzagoloff A (1979) Use of the UGA terminator as a tryptophan codon in yeast mitochondria. Proc Natl Acad Sci USA 76:3784–3785

    Google Scholar 

  • Masurekar M, Palmer E, Ono B-I, Wilhelm JM, Sherman F (1981) Misreading of the ribosomal suppressor SUP46 due to an altered 40S subunit in yeast. J Mol Biol 147:381–390

    Google Scholar 

  • McCready SJ, Cox BS (1973) Antisuppressors in yeast. Mol Gen Genet 124:305–320

    Google Scholar 

  • McCusker JH, Haber JE (1988) crl mutants of Saccharomyces cerevisiae resemble both mutants affecting general control of amino-acid biosynthesis and omnipotent translational suppressor mutants. Genetics 119:317–327

    Google Scholar 

  • Miller PF, Hinnebusch AG (1989) Sequences that surround the stop-codons of upstream open reading frames in GCN4 mRNA-determine their distinct functions in translational control. Genes Dev 3:1217–1225

    Google Scholar 

  • Millman G, Goldstein J, Scolnick E, Caskey CT (1969) Peptide termination III: stimulation of in-vitro termination. Proc Natl Acad Sci USA 63:183–190

    Google Scholar 

  • Mueller PP, Hinnebusch AG (1986) Multiple upstream AUG codons mediate translational control of GCN4. Cell 45:201–207

    Google Scholar 

  • Mueller PP, Trachsel H (1990) Translation and regulation of translation in the yeast Saccharomyces cerevisiae. Eur J Biochem 191:257–261

    Google Scholar 

  • Ono B-I, Stewart JW, Sherman F (1981) Serine insertion caused by the ribosomal suppressor SUP46 in yeast. J Mol Biol 147:373–379

    Google Scholar 

  • Ono B-I, Tanaka M, Kominami M, Ishino Y, Shinoda S (1982) Recessive UAA suppressors of the yeast Saccharomyces cerevisiae. Genetics 102:653–664

    Google Scholar 

  • Ono B-I, Moriga N, Ishihara K, Ishiguro J, Ishino Y, Shinoda S (1984) Omnipotent suppressors effective in [psi +] strains of Saccharomyces cervvisiae: recessiveness and dominance. Genetics 107:219–230

    Google Scholar 

  • Ono B-I, Ishino-Arao Y, Tanaka M, Awano I, Shinoda S (1986) Recessive nonsense suppressors in Saccharomyces cerevisae: action spectra, complementation groups and map positions. Genetics 114:363–374

    Google Scholar 

  • Ono B-I, Chernoff YO, Ishino-Arao Y, Yamagishi N, Shinoda S, Inge-Vechtomov SG (1991) Interactions between chromosomal omnipotent suppressors and extrachromosomal effectors in Saccharomyces cerevisiae. Curr Genet 19:243–248

    Google Scholar 

  • Ozaki M, Mizushima S, Nomura M (1969) Identification of the protein controlled by the streptomycin-resistance locus in E. coli. Nature 222:333–339

    Google Scholar 

  • Palmer E, Wilhelm JM, Sherman F (1979) Phenotypic suppression of nonsense mutants in yeast by aminoglycoside antibiotics. Nature 277:148–149

    Google Scholar 

  • Pel HJ, Maat C, Rep M, Grivell LA (1992) The yeast nuclear gene MRF1 encodes a mitochondrial peptide chain release factor and cures several mitochondrial RNA splicing defects. Nucleic Acids Res 20:6339–6346

    Google Scholar 

  • Pure GA, Robinson GW, Naumovski L, Friedberg EC (1985) Partial suppression of an ochre mutation in Saccharomyces cerevisiae by multicopy plasmids containing a normal tRNAgln gene. J Mol Biol 183:31–42

    Google Scholar 

  • Rosset R, Gorini L (1969) A ribosomal ambiguity mutation. J Mol Biol 39:95–107

    Google Scholar 

  • Scolnick E, Tompkins R, Caskey CT, Niremberg M (1968) Release factors differing in specificity for termination codons. Proc Natl Acad Sci USA 61:768–774

    Google Scholar 

  • Sherman F (1982) Suppression in the yeast Saccharomyces cerevisiae. In: Strathern J, Jones E, Broach J (eds) The molecular biology of the yeast Saccharomyces: metabolism and gene expression. Cold Spring Harbour Laboratory, Cold Spring Harbour, New York, pp 463–486

    Google Scholar 

  • Singh A, Ursic D, Davies J (1979) Phenotypic suppression and misreading in Saccharomyces cerevisiae. Nature 227:146–148

    Google Scholar 

  • Smirnov VN, Surguchov AP, Fominykch ES, Lizlova LV, Saprygina TV, Inge-Vechtomov SG (1976) Recessive nonsense suppression in yeast: further characterisation of a defect in translation. FEBS Lett 66:12–15

    Google Scholar 

  • Slobin LI (1980) The role of elongation factor Tu in protein synthesis. Eur J Biochem 110:555–563

    Google Scholar 

  • Song JM, Liebman SW (1987) Allosuppressors that enhance the efficiency of omnipotent suppressors in Saccharomyces cerevisiae. Genetics 115:451–460

    Google Scholar 

  • Stansfield I, Grant CM, Akhmaloka Tuite MF (1992) Ribosomal association of the yeast SAL4 (SUP45) gene product: implications for its role in translational fidelity and termination. Mol Microbiol 6:3469–3478

    Google Scholar 

  • Surguchov AP, Fominykch ES, Berestetskaya YV, Smirnov VN, Inge-Vechtomov SG (1980) Recessive nonsense-suppression in yeast Saccharomyces cerevisiae. Mol Gen Genet 177:675–680

    Google Scholar 

  • Surguchov AP, Telkov MV, Smirnov VN (1986) Absence of structural homology between SUP1 and SUP2 genes of yeast Saccharomyces cerevisiae and identification of their transcripts. FEBS Lett 206:147–150

    Google Scholar 

  • Tassan JP, Le Guellec K, Kress M, Faure M, Camonis J, Jacquet M, Philippe M (1993) In Xenopus laevis the product of a developmentally-regulated mRNA is structurally and functionally homologous to a Saccharomyces cerevisiae protein involved in translation fidelity. Mol Cell Biol 13:2815–2821

    Google Scholar 

  • Ter-Avanesyan MD, Kushnirov VV, Dagkesamanskaya AR, Didichenko SA, Chernoff YO, Inge-Vechtomov SG, Smirnov VN (1993) Deletion analysis of the SUP35 gene of the yeast Saccharomyces cerevisiae reveals two non-overlapping functional regions in the encoded protein. Mol Microbiol 7:683–692

    Google Scholar 

  • Tuite MF (1989) Protein synthesis. In: Rose AH, Harrison JS (eds) The yeasts, vol 3, 2nd edn. Academic Press, New York, pp 161–204

    Google Scholar 

  • Tuite MF, McLaughlin CS (1982) Natural readthrough of a UGA codon in a yeast cell-free system: evidence for involvement of both a mitochondrial and nuclear tRNA. Mol Cell Biol 2:490–497

    Google Scholar 

  • Tuite MF, Mundy CR, Cox BS (1981) Agents that cause a high frequency of genetic change from [psi +] to [psi -] in Saccharomyces cerevisiae. Genetics 98:691–711

    Google Scholar 

  • Tuite MF, Cox BS, McLaughlin CS (1987) A ribosome-associated inhibitor of in vitro nonsense suppression in [psi -] strains of yeast. FEBS Letts 225:205–208

    Google Scholar 

  • Tuite MF, Akhmaloka, Firoozan M, Duarte JAB, Grant CM (1990) Controlling translational accuracy in Saccharomyces cerevisiae: the molecular genetic analysis of a key translation factor, the Sal4 protein. In: McCarthy JEG, Tuite MF (eds) Post-transcriptional control of gene-expression. Springer, Berlin Heidelberg New York, pp 611–622

    Google Scholar 

  • Vincent A, Liebman SW (1992) The yeast omnipotent suppressor SUP46 encodes a ribosomal protein which is a functional and structural homolog of the Escherichia coli S4 ram protein. Genetics 132:375–386

    Google Scholar 

  • Weiss WA, Friedberg EC (1987) Normal yeast tRNAgln can suppress amber codons and is encoded by an essential gene. J Mol Biol 192:725–735

    Google Scholar 

  • Weiss RB, Murphy JP, Gallant JA (1984) Genetic screen for cloned release factor genes. J Bacteriol 158:362–364

    Google Scholar 

  • Wilson PG, Culbertson MR (1988) SUF12 suppressor protein of yeast: a fusion protein related to the EF-1 family of elongation factors. J Mol Biol 199:559–573

    Google Scholar 

  • Young CSH, Cox BS (1971) Extrachromosomal elements in a super-suppression strain of yeast. I. A nuclear gene controlling the inheritance of the extrachromosomal elements. Heredity 26:413–422

    Google Scholar 

  • Young CSH, Cox BS (1975) Extrachromosomal elements in a super-suppression strain of yeast. III. Enhanced detection of weak suppressors in certain non-suppressed strains. Heredity 34:83–92

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research School of Biosciences, University of Kent, CT2 7NJ, Canterbury, Kent, UK

    Ian Stansfield & Mick F. Tuite

Authors
  1. Ian Stansfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mick F. Tuite
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Communicated by L.A. Grivell

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stansfield, I., Tuite, M.F. Polypeptide chain termination in Saccharomyces cerevisiae . Curr Genet 25, 385–395 (1994). https://doi.org/10.1007/BF00351776

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00351776

Keywords

Search

Navigation