Skip to main content
RNA logoLink to RNA
. 1999 Nov;5(11):1451–1457. doi: 10.1017/s1355838299990490

Translational suppressors and antisuppressors alter the efficiency of the Ty1 programmed translational frameshift.

C L Burck 1, Y O Chernoff 1, R Liu 1, P J Farabaugh 1, S W Liebman 1
PMCID: PMC1369866  PMID: 10580473

Abstract

Certain viruses, transposons, and cellular genes have evolved specific sequences that induce high levels of specific translational errors. Such "programmed misreading" can result in levels of frameshifting or nonsense codon readthrough that are up to 1,000-fold higher than normal. Here we determine how a number of mutations in yeast affect the programmed misreading used by the yeast Ty retrotransposons. These mutations have previously been shown to affect the general accuracy of translational termination. We find that among four nonsense suppressor ribosomal mutations tested, one (a ribosomal protein mutation) enhanced the efficiency of the Tyl frameshifting, another (an rRNA mutation) reduced frameshifting, and two others (another ribosomal protein mutation and another rRNA mutation) had no effect. Three antisuppressor rRNA mutations all reduced Tyl frameshifting; however the antisuppressor mutation in the ribosomal protein did not show any effect. Among nonribosomal mutations, the allosuppressor protein phosphatase mutation enhanced Tyl frameshifting, whereas the partially inactive prion form of the release factor eRF3 caused a slight decrease, if any effect. A mutant form of the other release factor, eRF1, also had no effect on frameshifting. Our data suggest that Ty frameshifting is under the control of the cellular translational machinery. Surprisingly we find that translational suppressors can affect Ty frameshifting in either direction, whereas antisuppressors have either no effect or cause a decrease.

Full Text

The Full Text of this article is available as a PDF (317.3 KB).

Selected References

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

  1. Alksne L. E., Warner J. R. A novel cloning strategy reveals the gene for the yeast homologue to Escherichia coli ribosomal protein S12. J Biol Chem. 1993 May 25;268(15):10813–10819. [PubMed] [Google Scholar]
  2. All-Robyn J. A., Brown N., Otaka E., Liebman S. W. Sequence and functional similarity between a yeast ribosomal protein and the Escherichia coli S5 ram protein. Mol Cell Biol. 1990 Dec;10(12):6544–6553. doi: 10.1128/mcb.10.12.6544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. All-Robyn J. A., Kelley-Geraghty D., Griffin E., Brown N., Liebman S. W. Isolation of omnipotent suppressors in an [eta+] yeast strain. Genetics. 1990 Mar;124(3):505–514. doi: 10.1093/genetics/124.3.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Allen P. N., Noller H. F. Mutations in ribosomal proteins S4 and S12 influence the higher order structure of 16 S ribosomal RNA. J Mol Biol. 1989 Aug 5;208(3):457–468. doi: 10.1016/0022-2836(89)90509-3. [DOI] [PubMed] [Google Scholar]
  5. Andersson D. I., Andersson S. G., Kurland C. G. Functional interactions between mutated forms of ribosomal proteins S4, S5 and S12. Biochimie. 1986 May;68(5):705–713. doi: 10.1016/s0300-9084(86)80164-x. [DOI] [PubMed] [Google Scholar]
  6. Anthony R. A., Liebman S. W. Alterations in ribosomal protein RPS28 can diversely affect translational accuracy in Saccharomyces cerevisiae. Genetics. 1995 Aug;140(4):1247–1258. doi: 10.1093/genetics/140.4.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Arkov A. L., Freistroffer D. V., Ehrenberg M., Murgola E. J. Mutations in RNAs of both ribosomal subunits cause defects in translation termination. EMBO J. 1998 Mar 2;17(5):1507–1514. doi: 10.1093/emboj/17.5.1507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Belcourt M. F., Farabaugh P. J. Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on a 7 nucleotide minimal site. Cell. 1990 Jul 27;62(2):339–352. doi: 10.1016/0092-8674(90)90371-K. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bilgin N., Kirsebom L. A., Ehrenberg M., Kurland C. G. Mutations in ribosomal proteins L7/L12 perturb EF-G and EF-Tu functions. Biochimie. 1988 May;70(5):611–618. doi: 10.1016/0300-9084(88)90244-1. [DOI] [PubMed] [Google Scholar]
  10. Capel M. S., Engelman D. M., Freeborn B. R., Kjeldgaard M., Langer J. A., Ramakrishnan V., Schindler D. G., Schneider D. K., Schoenborn B. P., Sillers I. Y. A complete mapping of the proteins in the small ribosomal subunit of Escherichia coli. Science. 1987 Dec 4;238(4832):1403–1406. doi: 10.1126/science.3317832. [DOI] [PubMed] [Google Scholar]
  11. Chen M. X., Chen Y. H., Cohen P. T. PPQ, a novel protein phosphatase containing a Ser + Asn-rich amino-terminal domain, is involved in the regulation of protein synthesis. Eur J Biochem. 1993 Dec 1;218(2):689–699. doi: 10.1111/j.1432-1033.1993.tb18423.x. [DOI] [PubMed] [Google Scholar]
  12. Chernoff Y. O., Newnam G. P., Liebman S. W. The translational function of nucleotide C1054 in the small subunit rRNA is conserved throughout evolution: genetic evidence in yeast. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2517–2522. doi: 10.1073/pnas.93.6.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chernoff Y. O., Vincent A., Liebman S. W. Mutations in eukaryotic 18S ribosomal RNA affect translational fidelity and resistance to aminoglycoside antibiotics. EMBO J. 1994 Feb 15;13(4):906–913. doi: 10.1002/j.1460-2075.1994.tb06334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Clare J. J., Belcourt M., Farabaugh P. J. Efficient translational frameshifting occurs within a conserved sequence of the overlap between the two genes of a yeast Ty1 transposon. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6816–6820. doi: 10.1073/pnas.85.18.6816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Craigen W. J., Caskey C. T. Expression of peptide chain release factor 2 requires high-efficiency frameshift. Nature. 1986 Jul 17;322(6076):273–275. doi: 10.1038/322273a0. [DOI] [PubMed] [Google Scholar]
  16. Culbertson M. R., Gaber R. F., Cummins C. M. Frameshift suppression in Saccharomyces cerevisiae. V. Isolation and genetic properties of nongroup-specific suppressors. Genetics. 1982 Nov;102(3):361–378. doi: 10.1093/genetics/102.3.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Curcio M. J., Garfinkel D. J. Single-step selection for Ty1 element retrotransposition. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):936–940. doi: 10.1073/pnas.88.3.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Dinman J. D., Kinzy T. G. Translational misreading: mutations in translation elongation factor 1alpha differentially affect programmed ribosomal frameshifting and drug sensitivity. RNA. 1997 Aug;3(8):870–881. [PMC free article] [PubMed] [Google Scholar]
  19. Dinman J. D., Wickner R. B. 5 S rRNA is involved in fidelity of translational reading frame. Genetics. 1995 Sep;141(1):95–105. doi: 10.1093/genetics/141.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dinman J. D., Wickner R. B. Translational maintenance of frame: mutants of Saccharomyces cerevisiae with altered -1 ribosomal frameshifting efficiencies. Genetics. 1994 Jan;136(1):75–86. doi: 10.1093/genetics/136.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ehrenberg M., Kurland C. G., Ruusala T. Counting cycles of EF-Tu to measure proofreading in translation. Biochimie. 1986 Mar;68(2):261–273. doi: 10.1016/s0300-9084(86)80023-2. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Farabaugh P. J. Post-transcriptional regulation of transposition by Ty retrotransposons of Saccharomyces cerevisiae. J Biol Chem. 1995 May 5;270(18):10361–10364. doi: 10.1074/jbc.270.18.10361. [DOI] [PubMed] [Google Scholar]
  24. Farabaugh P. J. Programmed translational frameshifting. Annu Rev Genet. 1996;30:507–528. doi: 10.1146/annurev.genet.30.1.507. [DOI] [PubMed] [Google Scholar]
  25. Farabaugh P. J., Vimaladithan A. Effect of frameshift-inducing mutants of elongation factor 1alpha on programmed +1 frameshifting in yeast. RNA. 1998 Jan;4(1):38–46. [PMC free article] [PubMed] [Google Scholar]
  26. Farabaugh P. J., Zhao H., Vimaladithan A. A novel programed frameshift expresses the POL3 gene of retrotransposon Ty3 of yeast: frameshifting without tRNA slippage. Cell. 1993 Jul 16;74(1):93–103. doi: 10.1016/0092-8674(93)90297-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gesteland R. F., Atkins J. F. Recoding: dynamic reprogramming of translation. Annu Rev Biochem. 1996;65:741–768. doi: 10.1146/annurev.bi.65.070196.003521. [DOI] [PubMed] [Google Scholar]
  28. Glück A., Endo Y., Wool I. G. The ribosomal RNA identity elements for ricin and for alpha-sarcin: mutations in the putative CG pair that closes a GAGA tetraloop. Nucleic Acids Res. 1994 Feb 11;22(3):321–324. doi: 10.1093/nar/22.3.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Huang W. M., Ao S. Z., Casjens S., Orlandi R., Zeikus R., Weiss R., Winge D., Fang M. A persistent untranslated sequence within bacteriophage T4 DNA topoisomerase gene 60. Science. 1988 Feb 26;239(4843):1005–1012. doi: 10.1126/science.2830666. [DOI] [PubMed] [Google Scholar]
  30. Jacks T., Power M. D., Masiarz F. R., Luciw P. A., Barr P. J., Varmus H. E. Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature. 1988 Jan 21;331(6153):280–283. doi: 10.1038/331280a0. [DOI] [PubMed] [Google Scholar]
  31. Jacks T., Townsley K., Varmus H. E., Majors J. Two efficient ribosomal frameshifting events are required for synthesis of mouse mammary tumor virus gag-related polyproteins. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4298–4302. doi: 10.1073/pnas.84.12.4298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Jacks T., Varmus H. E. Expression of the Rous sarcoma virus pol gene by ribosomal frameshifting. Science. 1985 Dec 13;230(4731):1237–1242. doi: 10.1126/science.2416054. [DOI] [PubMed] [Google Scholar]
  33. Jain V. K., Magrath I. T. A chemiluminescent assay for quantitation of beta-galactosidase in the femtogram range: application to quantitation of beta-galactosidase in lacZ-transfected cells. Anal Biochem. 1991 Nov 15;199(1):119–124. doi: 10.1016/0003-2697(91)90278-2. [DOI] [PubMed] [Google Scholar]
  34. Kawakami K., Pande S., Faiola B., Moore D. P., Boeke J. D., Farabaugh P. J., Strathern J. N., Nakamura Y., Garfinkel D. J. A rare tRNA-Arg(CCU) that regulates Ty1 element ribosomal frameshifting is essential for Ty1 retrotransposition in Saccharomyces cerevisiae. Genetics. 1993 Oct;135(2):309–320. doi: 10.1093/genetics/135.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Liebman S. W., Derkatch I. L. The yeast [PSI+] prion: making sense of nonsense. J Biol Chem. 1999 Jan 15;274(3):1181–1184. doi: 10.1074/jbc.274.3.1181. [DOI] [PubMed] [Google Scholar]
  36. Liebman S. W., Sherman F. Extrachromosomal psi+ determinant suppresses nonsense mutations in yeast. J Bacteriol. 1979 Sep;139(3):1068–1071. doi: 10.1128/jb.139.3.1068-1071.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Liu R., Liebman S. W. A translational fidelity mutation in the universally conserved sarcin/ricin domain of 25S yeast ribosomal RNA. RNA. 1996 Mar;2(3):254–263. [PMC free article] [PubMed] [Google Scholar]
  38. Melançon P., Tapprich W. E., Brakier-Gingras L. Single-base mutations at position 2661 of Escherichia coli 23S rRNA increase efficiency of translational proofreading. J Bacteriol. 1992 Dec;174(24):7896–7901. doi: 10.1128/jb.174.24.7896-7901.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Moazed D., Robertson J. M., Noller H. F. Interaction of elongation factors EF-G and EF-Tu with a conserved loop in 23S RNA. Nature. 1988 Jul 28;334(6180):362–364. doi: 10.1038/334362a0. [DOI] [PubMed] [Google Scholar]
  40. Morikawa S., Booth T. F., Bishop D. H. Analyses of the requirements for the synthesis of virus-like particles by feline immunodeficiency virus gag using baculovirus vectors. Virology. 1991 Jul;183(1):288–297. doi: 10.1016/0042-6822(91)90141-w. [DOI] [PubMed] [Google Scholar]
  41. Murgola E. J., Hijazi K. A., Göringer H. U., Dahlberg A. E. Mutant 16S ribosomal RNA: a codon-specific translational suppressor. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4162–4165. doi: 10.1073/pnas.85.12.4162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Noller H. F., Hoffarth V., Zimniak L. Unusual resistance of peptidyl transferase to protein extraction procedures. Science. 1992 Jun 5;256(5062):1416–1419. doi: 10.1126/science.1604315. [DOI] [PubMed] [Google Scholar]
  43. Noller H. F. tRNA-rRNA interactions and peptidyl transferase. FASEB J. 1993 Jan;7(1):87–89. doi: 10.1096/fasebj.7.1.8422979. [DOI] [PubMed] [Google Scholar]
  44. O'Connor M., Göringer H. U., Dahlberg A. E. A ribosomal ambiguity mutation in the 530 loop of E. coli 16S rRNA. Nucleic Acids Res. 1992 Aug 25;20(16):4221–4227. doi: 10.1093/nar/20.16.4221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Pagel F. T., Zhao S. Q., Hijazi K. A., Murgola E. J. Phenotypic heterogeneity of mutational changes at a conserved nucleotide in 16 S ribosomal RNA. J Mol Biol. 1997 Apr 18;267(5):1113–1123. doi: 10.1006/jmbi.1997.0943. [DOI] [PubMed] [Google Scholar]
  46. Pande S., Vimaladithan A., Zhao H., Farabaugh P. J. Pulling the ribosome out of frame by +1 at a programmed frameshift site by cognate binding of aminoacyl-tRNA. Mol Cell Biol. 1995 Jan;15(1):298–304. doi: 10.1128/mcb.15.1.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sandbaken M. G., Culbertson M. R. Mutations in elongation factor EF-1 alpha affect the frequency of frameshifting and amino acid misincorporation in Saccharomyces cerevisiae. Genetics. 1988 Dec;120(4):923–934. doi: 10.1093/genetics/120.4.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Song J. M., Liebman S. W. Allosuppressors that enhance the efficiency of omnipotent suppressors in Saccharomyces cerevisiae. Genetics. 1987 Mar;115(3):451–460. doi: 10.1093/genetics/115.3.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. Synetos D., Frantziou C. P., Alksne L. E. Mutations in yeast ribosomal proteins S28 and S4 affect the accuracy of translation and alter the sensitivity of the ribosomes to paromomycin. Biochim Biophys Acta. 1996 Nov 11;1309(1-2):156–166. doi: 10.1016/s0167-4781(96)00128-5. [DOI] [PubMed] [Google Scholar]
  51. Szewczak A. A., Moore P. B., Chang Y. L., Wool I. G. The conformation of the sarcin/ricin loop from 28S ribosomal RNA. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9581–9585. doi: 10.1073/pnas.90.20.9581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. 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]
  53. Vimaladithan A., Farabaugh P. J. Special peptidyl-tRNA molecules can promote translational frameshifting without slippage. Mol Cell Biol. 1994 Dec;14(12):8107–8116. doi: 10.1128/mcb.14.12.8107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Vincent A., Newnam G., Liebman S. W. The yeast translational allosuppressor, SAL6: a new member of the PP1-like phosphatase family with a long serine-rich N-terminal extension. Genetics. 1994 Nov;138(3):597–608. doi: 10.1093/genetics/138.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Weiss R. B., Huang W. M., Dunn D. M. A nascent peptide is required for ribosomal bypass of the coding gap in bacteriophage T4 gene 60. Cell. 1990 Jul 13;62(1):117–126. doi: 10.1016/0092-8674(90)90245-A. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wickner R. B. Double-stranded and single-stranded RNA viruses of Saccharomyces cerevisiae. Annu Rev Microbiol. 1992;46:347–375. doi: 10.1146/annurev.mi.46.100192.002023. [DOI] [PubMed] [Google Scholar]
  57. Wickner R. B., Edskes H. K., Maddelein M. L., Taylor K. L., Moriyama H. Prions of yeast and fungi. Proteins as genetic material. J Biol Chem. 1999 Jan 8;274(2):555–558. doi: 10.1074/jbc.274.2.555. [DOI] [PubMed] [Google Scholar]
  58. 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]
  59. Wool I. G., Glück A., Endo Y. Ribotoxin recognition of ribosomal RNA and a proposal for the mechanism of translocation. Trends Biochem Sci. 1992 Jul;17(7):266–269. doi: 10.1016/0968-0004(92)90407-z. [DOI] [PubMed] [Google Scholar]
  60. 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]

Articles from RNA are provided here courtesy of The RNA Society

RESOURCES