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. 1996 Mar 15;15(6):1360–1370.

Reading two bases twice: mammalian antizyme frameshifting in yeast.

S Matsufuji 1, T Matsufuji 1, N M Wills 1, R F Gesteland 1, J F Atkins 1
PMCID: PMC450040  PMID: 8635469

Abstract

Programmed translational frameshifting is essential for the expression of mammalian ornithine decarboxylase antizyme, a protein involved in the regulation of intracellular polyamines. A cassette containing antizyme frameshift signals is found to direct high-level (16%) frameshifting in yeast, Saccharomyces cerevisiae. In contrast to +1 frameshifting in the mammalian system, in yeast the same frame is reached by -2 frameshifting. Two bases are read twice. The -2 frameshifting is likely to be mediated by slippage of mRNA and re-pairing with the tRNA in the P-site. The downstream pseudoknot stimulates frameshifting by 30-fold compared with 2.5-fold in reticulocyte lysates. When the length of the spacer between the shift site and the pseudoknot is extended by three nucleotides, +1 and -2 frameshifting become equal.

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Selected References

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  1. Balasundaram D., Dinman J. D., Tabor C. W., Tabor H. SPE1 and SPE2: two essential genes in the biosynthesis of polyamines that modulate +1 ribosomal frameshifting in Saccharomyces cerevisiae. J Bacteriol. 1994 Nov;176(22):7126–7128. doi: 10.1128/jb.176.22.7126-7128.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balasundaram D., Dinman J. D., Wickner R. B., Tabor C. W., Tabor H. Spermidine deficiency increases +1 ribosomal frameshifting efficiency and inhibits Ty1 retrotransposition in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):172–176. doi: 10.1073/pnas.91.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Benhar I., Engelberg-Kulka H. A procedure for amino acid sequencing in internal regions of proteins. Gene. 1991 Jul 15;103(1):79–82. doi: 10.1016/0378-1119(91)90394-q. [DOI] [PubMed] [Google Scholar]
  5. Blinkowa A. L., Walker J. R. Programmed ribosomal frameshifting generates the Escherichia coli DNA polymerase III gamma subunit from within the tau subunit reading frame. Nucleic Acids Res. 1990 Apr 11;18(7):1725–1729. doi: 10.1093/nar/18.7.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brierley I., Jenner A. J., Inglis S. C. Mutational analysis of the "slippery-sequence" component of a coronavirus ribosomal frameshifting signal. J Mol Biol. 1992 Sep 20;227(2):463–479. doi: 10.1016/0022-2836(92)90901-U. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brierley I., Rolley N. J., Jenner A. J., Inglis S. C. Mutational analysis of the RNA pseudoknot component of a coronavirus ribosomal frameshifting signal. J Mol Biol. 1991 Aug 20;220(4):889–902. doi: 10.1016/0022-2836(91)90361-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chandler M., Fayet O. Translational frameshifting in the control of transposition in bacteria. Mol Microbiol. 1993 Feb;7(4):497–503. doi: 10.1111/j.1365-2958.1993.tb01140.x. [DOI] [PubMed] [Google Scholar]
  9. Chen X., Chamorro M., Lee S. I., Shen L. X., Hines J. V., Tinoco I., Jr, Varmus H. E. Structural and functional studies of retroviral RNA pseudoknots involved in ribosomal frameshifting: nucleotides at the junction of the two stems are important for efficient ribosomal frameshifting. EMBO J. 1995 Feb 15;14(4):842–852. doi: 10.1002/j.1460-2075.1995.tb07062.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Curran J. F. Decoding with the A:I wobble pair is inefficient. Nucleic Acids Res. 1995 Feb 25;23(4):683–688. doi: 10.1093/nar/23.4.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Di R., Dinesh-Kumar S. P., Miller W. A. Translational frameshifting by barley yellow dwarf virus RNA (PAV serotype) in Escherichia coli and in eukaryotic cell-free extracts. Mol Plant Microbe Interact. 1993 Jul-Aug;6(4):444–452. doi: 10.1094/mpmi-6-444. [DOI] [PubMed] [Google Scholar]
  12. Dinman J. D., Icho T., Wickner R. B. A -1 ribosomal frameshift in a double-stranded RNA virus of yeast forms a gag-pol fusion protein. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):174–178. doi: 10.1073/pnas.88.1.174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Donly B. C., Tate W. P. Frameshifting by eukaryotic ribosomes during expression of Escherichia coli release factor 2. Proc Biol Sci. 1991 Jun 22;244(1311):207–210. doi: 10.1098/rspb.1991.0072. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Flower A. M., McHenry C. S. The gamma subunit of DNA polymerase III holoenzyme of Escherichia coli is produced by ribosomal frameshifting. Proc Natl Acad Sci U S A. 1990 May;87(10):3713–3717. doi: 10.1073/pnas.87.10.3713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fong W. F., Heller J. S., Canellakis E. S. The appearance of an ornithine decarboxylase inhibitory protein upon the addition of putrescine to cell cultures. Biochim Biophys Acta. 1976 Apr 23;428(2):456–465. doi: 10.1016/0304-4165(76)90054-4. [DOI] [PubMed] [Google Scholar]
  19. Fonzi W. A. Regulation of Saccharomyces cerevisiae ornithine decarboxylase expression in response to polyamine. J Biol Chem. 1989 Oct 25;264(30):18110–18118. [PubMed] [Google Scholar]
  20. Garcia A., van Duin J., Pleij C. W. Differential response to frameshift signals in eukaryotic and prokaryotic translational systems. Nucleic Acids Res. 1993 Feb 11;21(3):401–406. doi: 10.1093/nar/21.3.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gesteland R. F., Weiss R. B., Atkins J. F. Recoding: reprogrammed genetic decoding. Science. 1992 Sep 18;257(5077):1640–1641. doi: 10.1126/science.1529352. [DOI] [PubMed] [Google Scholar]
  22. Gillman E. C., Slusher L. B., Martin N. C., Hopper A. K. MOD5 translation initiation sites determine N6-isopentenyladenosine modification of mitochondrial and cytoplasmic tRNA. Mol Cell Biol. 1991 May;11(5):2382–2390. doi: 10.1128/mcb.11.5.2382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Guarente L. Yeast promoters and lacZ fusions designed to study expression of cloned genes in yeast. Methods Enzymol. 1983;101:181–191. doi: 10.1016/0076-6879(83)01013-7. [DOI] [PubMed] [Google Scholar]
  24. Hatfield D. L., Levin J. G., Rein A., Oroszlan S. Translational suppression in retroviral gene expression. Adv Virus Res. 1992;41:193–239. doi: 10.1016/S0065-3527(08)60037-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hayashi S., Murakami Y. Rapid and regulated degradation of ornithine decarboxylase. Biochem J. 1995 Feb 15;306(Pt 1):1–10. doi: 10.1042/bj3060001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Horsfield J. A., Wilson D. N., Mannering S. A., Adamski F. M., Tate W. P. Prokaryotic ribosomes recode the HIV-1 gag-pol-1 frameshift sequence by an E/P site post-translocation simultaneous slippage mechanism. Nucleic Acids Res. 1995 May 11;23(9):1487–1494. doi: 10.1093/nar/23.9.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ichiba T., Matsufuji S., Miyazaki Y., Hayashi S. Nucleotide sequence of ornithine decarboxylase antizyme cDNA from Xenopus laevis. Biochim Biophys Acta. 1995 May 17;1262(1):83–86. doi: 10.1016/0167-4781(95)00062-l. [DOI] [PubMed] [Google Scholar]
  28. Ichiba T., Matsufuji S., Miyazaki Y., Murakami Y., Tanaka K., Ichihara A., Hayashi S. Functional regions of ornithine decarboxylase antizyme. Biochem Biophys Res Commun. 1994 May 16;200(3):1721–1727. doi: 10.1006/bbrc.1994.1651. [DOI] [PubMed] [Google Scholar]
  29. 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. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kane J. F., Violand B. N., Curran D. F., Staten N. R., Duffin K. L., Bogosian G. Novel in-frame two codon translational hop during synthesis of bovine placental lactogen in a recombinant strain of Escherichia coli. Nucleic Acids Res. 1992 Dec 25;20(24):6707–6712. doi: 10.1093/nar/20.24.6707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  33. Larsen B., Wills N. M., Gesteland R. F., Atkins J. F. rRNA-mRNA base pairing stimulates a programmed -1 ribosomal frameshift. J Bacteriol. 1994 Nov;176(22):6842–6851. doi: 10.1128/jb.176.22.6842-6851.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lee S. I., Umen J. G., Varmus H. E. A genetic screen identifies cellular factors involved in retroviral -1 frameshifting. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6587–6591. doi: 10.1073/pnas.92.14.6587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Li X., Coffino P. Distinct domains of antizyme required for binding and proteolysis of ornithine decarboxylase. Mol Cell Biol. 1994 Jan;14(1):87–92. doi: 10.1128/mcb.14.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lindsley D., Gallant J. On the directional specificity of ribosome frameshifting at a "hungry" codon. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5469–5473. doi: 10.1073/pnas.90.12.5469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Matsudaira P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem. 1987 Jul 25;262(21):10035–10038. [PubMed] [Google Scholar]
  38. Matsufuji S., Matsufuji T., Miyazaki Y., Murakami Y., Atkins J. F., Gesteland R. F., Hayashi S. Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme. Cell. 1995 Jan 13;80(1):51–60. doi: 10.1016/0092-8674(95)90450-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Matsufuji S., Miyazaki Y., Kanamoto R., Kameji T., Murakami Y., Baby T. G., Fujita K., Ohno T., Hayashi S. Analyses of ornithine decarboxylase antizyme mRNA with a cDNA cloned from rat liver. J Biochem. 1990 Sep;108(3):365–371. doi: 10.1093/oxfordjournals.jbchem.a123207. [DOI] [PubMed] [Google Scholar]
  40. Mierendorf R. C., Percy C., Young R. A. Gene isolation by screening lambda gt11 libraries with antibodies. Methods Enzymol. 1987;152:458–469. doi: 10.1016/0076-6879(87)52054-7. [DOI] [PubMed] [Google Scholar]
  41. Mitchell J. L., Judd G. G., Bareyal-Leyser A., Ling S. Y. Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells. Biochem J. 1994 Apr 1;299(Pt 1):19–22. doi: 10.1042/bj2990019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Miyazaki Y., Matsufuji S., Hayashi S. Cloning and characterization of a rat gene encoding ornithine decarboxylase antizyme. Gene. 1992 Apr 15;113(2):191–197. doi: 10.1016/0378-1119(92)90395-6. [DOI] [PubMed] [Google Scholar]
  43. Murakami Y., Matsufuji S., Kameji T., Hayashi S., Igarashi K., Tamura T., Tanaka K., Ichihara A. Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination. Nature. 1992 Dec 10;360(6404):597–599. doi: 10.1038/360597a0. [DOI] [PubMed] [Google Scholar]
  44. Polard P., Prère M. F., Chandler M., Fayet O. Programmed translational frameshifting and initiation at an AUU codon in gene expression of bacterial insertion sequence IS911. J Mol Biol. 1991 Dec 5;222(3):465–477. doi: 10.1016/0022-2836(91)90490-w. [DOI] [PubMed] [Google Scholar]
  45. Rom E., Kahana C. Polyamines regulate the expression of ornithine decarboxylase antizyme in vitro by inducing ribosomal frame-shifting. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3959–3963. doi: 10.1073/pnas.91.9.3959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Rose M., Botstein D. Construction and use of gene fusions to lacZ (beta-galactosidase) that are expressed in yeast. Methods Enzymol. 1983;101:167–180. doi: 10.1016/0076-6879(83)01012-5. [DOI] [PubMed] [Google Scholar]
  47. Schena M., Picard D., Yamamoto K. R. Vectors for constitutive and inducible gene expression in yeast. Methods Enzymol. 1991;194:389–398. doi: 10.1016/0076-6879(91)94029-c. [DOI] [PubMed] [Google Scholar]
  48. Shen L. X., Tinoco I., Jr The structure of an RNA pseudoknot that causes efficient frameshifting in mouse mammary tumor virus. J Mol Biol. 1995 Apr 14;247(5):963–978. doi: 10.1006/jmbi.1995.0193. [DOI] [PubMed] [Google Scholar]
  49. Somogyi P., Jenner A. J., Brierley I., Inglis S. C. Ribosomal pausing during translation of an RNA pseudoknot. Mol Cell Biol. 1993 Nov;13(11):6931–6940. doi: 10.1128/mcb.13.11.6931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Stahl G., Bidou L., Rousset J. P., Cassan M. Versatile vectors to study recoding: conservation of rules between yeast and mammalian cells. Nucleic Acids Res. 1995 May 11;23(9):1557–1560. doi: 10.1093/nar/23.9.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Suzuki T., He Y., Kashiwagi K., Murakami Y., Hayashi S., Igarashi K. Antizyme protects against abnormal accumulation and toxicity of polyamines in ornithine decarboxylase-overproducing cells. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8930–8934. doi: 10.1073/pnas.91.19.8930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Tai J. H., Ip C. F. The cDNA sequence of Trichomonas vaginalis virus-T1 double-stranded RNA. Virology. 1995 Jan 10;206(1):773–776. doi: 10.1016/s0042-6822(95)80008-5. [DOI] [PubMed] [Google Scholar]
  53. Tewari D. S., Qian Y., Thornton R. D., Pieringer J., Taub R., Mochan E., Tewari M. Molecular cloning and sequencing of a human cDNA encoding ornithine decarboxylase antizyme. Biochim Biophys Acta. 1994 Dec 14;1209(2):293–295. doi: 10.1016/0167-4838(94)90199-6. [DOI] [PubMed] [Google Scholar]
  54. Tsuchihashi Z., Brown P. O. Sequence requirements for efficient translational frameshifting in the Escherichia coli dnaX gene and the role of an unstable interaction between tRNA(Lys) and an AAG lysine codon. Genes Dev. 1992 Mar;6(3):511–519. doi: 10.1101/gad.6.3.511. [DOI] [PubMed] [Google Scholar]
  55. Tsuchihashi Z., Kornberg A. Translational frameshifting generates the gamma subunit of DNA polymerase III holoenzyme. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2516–2520. doi: 10.1073/pnas.87.7.2516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Tsuchihashi Z. Translational frameshifting in the Escherichia coli dnaX gene in vitro. Nucleic Acids Res. 1991 May 11;19(9):2457–2462. doi: 10.1093/nar/19.9.2457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Tu C., Tzeng T. H., Bruenn J. A. Ribosomal movement impeded at a pseudoknot required for frameshifting. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8636–8640. doi: 10.1073/pnas.89.18.8636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Tzeng T. H., Tu C. L., Bruenn J. A. Ribosomal frameshifting requires a pseudoknot in the Saccharomyces cerevisiae double-stranded RNA virus. J Virol. 1992 Feb;66(2):999–1006. doi: 10.1128/jvi.66.2.999-1006.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Weiss R. B., Dunn D. M., Atkins J. F., Gesteland R. F. Ribosomal frameshifting from -2 to +50 nucleotides. Prog Nucleic Acid Res Mol Biol. 1990;39:159–183. doi: 10.1016/s0079-6603(08)60626-1. [DOI] [PubMed] [Google Scholar]
  60. Weiss R. B., Dunn D. M., Atkins J. F., Gesteland R. F. Slippery runs, shifty stops, backward steps, and forward hops: -2, -1, +1, +2, +5, and +6 ribosomal frameshifting. Cold Spring Harb Symp Quant Biol. 1987;52:687–693. doi: 10.1101/sqb.1987.052.01.078. [DOI] [PubMed] [Google Scholar]
  61. Weiss R. B., Dunn D. M., Shuh M., Atkins J. F., Gesteland R. F. E. coli ribosomes re-phase on retroviral frameshift signals at rates ranging from 2 to 50 percent. New Biol. 1989 Nov;1(2):159–169. [PubMed] [Google Scholar]
  62. Wilson W., Braddock M., Adams S. E., Rathjen P. D., Kingsman S. M., Kingsman A. J. HIV expression strategies: ribosomal frameshifting is directed by a short sequence in both mammalian and yeast systems. Cell. 1988 Dec 23;55(6):1159–1169. doi: 10.1016/0092-8674(88)90260-7. [DOI] [PubMed] [Google Scholar]
  63. Xu H., Boeke J. D. Host genes that influence transposition in yeast: the abundance of a rare tRNA regulates Ty1 transposition frequency. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8360–8364. doi: 10.1073/pnas.87.21.8360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Yelverton E., Lindsley D., Yamauchi P., Gallant J. A. The function of a ribosomal frameshifting signal from human immunodeficiency virus-1 in Escherichia coli. Mol Microbiol. 1994 Jan;11(2):303–313. doi: 10.1111/j.1365-2958.1994.tb00310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. de Smit M. H., van Duin J., van Knippenberg P. H., van Eijk H. G. CCC.UGA: a new site of ribosomal frameshifting in Escherichia coli. Gene. 1994 May 27;143(1):43–47. doi: 10.1016/0378-1119(94)90602-5. [DOI] [PubMed] [Google Scholar]

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