UAG Suppressor Glutamine tRNA in Uninfected and Retrovirus-Infected Mammalian Cells

  • Y. Kuchino
  • S. Nishimura
  • H. C. Schröder
  • W. E. G. Müller
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 11)


Three codons, UAG, UAA, and UGA, in the genetic code are normally signals for termination of translation reaction and for the release of the completed polypeptide chain from its ultimate ribosome-bound tRNA. Recently, it has been reported that eubacterial and eukaryotic mRNAs contain a translatable nonsense codon and its readthrough by suppressor tRNA plays an important role in the synthesis of particular proteins which are necessary for specific cellular functions. For example, in-frame UGA nonsense codons have been found in the mouse glutathione peroxidase and Escherichia coli formate dehydrogenase genes (Chambers et al. 1986; Zinoni et al. 1986). The translational insertion of selenocystein at the UGA codon, which is the active site of the enzymes from those genes, is required for the expression of their enzyme activities. The internal nonsense codons have also been detected at the gag-pol junction of the retrovirus genomes, such as Moloney murine leukemia virus (Mo-MuLV) and Rous sarcoma virus (RSV) (Shinnick et al. 1981; Phillipson et al. 1978; Yoshinaka et al. 1985; Crawford and Goff 1985; Jacks and Varmus 1985). The readthrough of the nonsense codon produces a viral gag-pol precursor fusion protein which is later cleaved by proteases to yield the mature viral proteins, including protease. The translation of the internal nonsense codon of the retrovirus genomes so far reported is performed by nonsense suppression or frameshift suppression, resulting in the regulation of the level of gag and gag-pol readthrough proteins in the virus-infected cells, which is required for the vegetative virus proliferation.


Termination Codon Rous Sarcoma Virus Rabbit Reticulocyte Lysate Nonsense Suppression Nonsense Codon 
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  1. Beier H, Barciszewska M, Krupp G, Mitnacht R, Gross HJ (1984) UAG readthrough during TMV RNA translation: isolation and sequence of two tRNAsTyr with suppressor activity from tobacco plants. EMBO J 3: 351–356PubMedGoogle Scholar
  2. Craigen WJ, Caskey CT (1987) Translational frameshifting: where will it stop? Cell 50: 1–2PubMedCrossRefGoogle Scholar
  3. Caron F, Meyer E (1985) Does Paramecium primaurelia use a different genetic code in its macronucleus? Nature 314: 185–188PubMedCrossRefGoogle Scholar
  4. Chambers I, Frampton J, Goldfarb P, Affara N, McBain W, Harrison PR (1986) The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the ‘termination’ codon, TGA. EMBO J 5: 1221–1227Google Scholar
  5. Crawford S, Goff SP (1985) A deletion mutation in the 5’ part of the pol gene of Moloney murine leukemia virus blocks proteolytic processing of the gag and pol polyproteins. J Virol 53: 899–907PubMedGoogle Scholar
  6. Hanyu N, Kuchino Y, Nishimura S, Beier H (1986) Dramatic events in ciliate evolution: alteration of UAA and UAG termination codons to glutamine codons due to anticodon mutations in two Tetrahymena tRNAsG’n. EMBOJ 5: 1307–1311Google Scholar
  7. Helftenbein E (1985) Nucleotide sequence of a macronuclear DNA molecule coding for atubulin from the ciliate Stylonychia lemnae. Special codon usage: TAA is not a translation termination codon. Nucleic Acids Res 13: 415–433PubMedCrossRefGoogle Scholar
  8. Herr W (1984) Nucleotide sequence of AKV murine leukemia virus. J Virol 49: 471–478PubMedGoogle Scholar
  9. Horowitz S, Gorovsky MA (1985) An unusual genetic code in nuclear genes of Tetrahymena. Proc Natl Acad Sci USA 82: 2452–2455PubMedCrossRefGoogle Scholar
  10. Jacks T, Varmus HE (1985) Expression of the Rous sarcoma virus pol gene by ribosomal frameshifting. Science 230: 1237–1242PubMedCrossRefGoogle Scholar
  11. Jacks T, Townsley K, Varmus HE, Majors J (1987) Two efficient ribosomal frameshifting events are required for synthesis of mouse mammary tumor virus gag-related polyproteins. Proc Natl Acad Sci USA 84: 4298–4302PubMedCrossRefGoogle Scholar
  12. Jacks T, Power MD, Masiarz FR, Luciw PA, Barr PJ, Varmus HE (1988) Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature 331: 280–283PubMedCrossRefGoogle Scholar
  13. Kaine BP, Spear BB (1982) Nucleotide sequence of a macronuclear gene for actin in Oxytricha fallax. Nature 295: 430–432PubMedCrossRefGoogle Scholar
  14. Keith G (1984) The primary structures of two arginine tRNAs (anticodons CCU and mcro5a2UCi/i) and of glutamine tRNA (anticodon CUG) from bovine liver. Nucleic Acids Res 12: 2543–2547PubMedCrossRefGoogle Scholar
  15. Kuchino Y, Hanyu N, Tashiro F, Nishimura S (1985) Tetrahymena thermophila glutamine tRNA and its gene that corresponds to UAA termination codon. Proc Natl Acad Sci USA 82: 4758–4762PubMedCrossRefGoogle Scholar
  16. Kuchino Y, Beier H, Akita N, Nishimura S (1987a) Natural UAG suppressor glutamine tRNA is elevated in mouse cells infected with Moloney murine leukemia virus. Proc Natl Acad Sci USA 84: 2668–2672PubMedCrossRefGoogle Scholar
  17. Kuchino Y, Hanyu N, Nishimura S (1987b) Analysis of modified nucleosides and nucleotide sequence of tRNA. Methods Enzymol 155: 379–396PubMedCrossRefGoogle Scholar
  18. Kuchino Y, Nishimura S, Schröder HC, Rottmann M, Müller WEG (1988) Selective inhibition of formation of suppressor glutamine tRNA in Moloney murine leukemia virus-infected NIH-3T3 cells by Avarol. Virology 165: 518–526PubMedCrossRefGoogle Scholar
  19. Maruyama T, Gojobori T, Aota S, Ikemura T (1986) Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res 14: 151–197Google Scholar
  20. Mailer WEG, Sarin PS, Kuchino Y, Dorn A, Hess G, Meyer zum Büschenfelde K-H, Rottmann M, Schröder HC (1987) Avarol, a novel anti-HIV compound, which modulates posttranscriptional control systems. In: Vettermann W, Schauzu M (eds) AIDS, Bundesministerium für Forschung and Technologie, Bonn, pp. 354–378Google Scholar
  21. Müller WEG, Schröder, HC, Reuter P, Sarin PS, Hess G, Meyer zum Büschenfelde K-H, Kuchino Y, Nishimura S (1988) Inhibition of expression of natural UAG suppressor glutamine tRNA in HIV-infected human H9 cells in vitro by Avarol. AIDS Res & Human Retrovirus 4: 279–286CrossRefGoogle Scholar
  22. O’Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250: 4007–4021PubMedGoogle Scholar
  23. Phillipson L, Andersson P, Olshevsky U, Weinberg R, Baltimore D, Gesteland R (1978) Translation of MuLV and MSV RNAs in nuclease-treated reticulocyte extracts: enhancements of the gag-pol polypeptide with yeast suppressor tRNA. Cell 13: 189–199CrossRefGoogle Scholar
  24. Preer JR Jr, Preer LB, Rudman BM, Barnett AJ (1985) Deviation from the universal code shown by the gene for surface protein 51A in Paramecium. Nature 314: 188–190PubMedCrossRefGoogle Scholar
  25. Pure GA, Robinson GW, Naumovski L, Friedberg EC (1985) Partial suppression of an ochre mutation in Saccharomyces cerevisiae by multicopy plasmids containing a normal yeast tRNAGln gene. J Mol Biol 183: 31–42PubMedCrossRefGoogle Scholar
  26. Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, Ivanoff L, Petteway SRJr, Pearson ML, Lautenberger JA, Papas TS, Ghrayeb J, Chang NT, Gallo RC, Wong-Staal F (1985) Complete nucleotide sequence of the AIDS virus, HTVL-III. Nature 313: 277–284Google Scholar
  27. Roy KL, Cooke H, Buckland R (1982) Nucleotide sequence of a segment of human DNA containing the three tRNA genes. Nucleic Acids Res 10: 7313–7322PubMedCrossRefGoogle Scholar
  28. Schweyen RJ, Wolf K, Kaudewita F (1983) Mitochondria 1983, Nucleo-mitochondrial interactions. de Gruyter, Berlin, FRG, pp 1–648Google Scholar
  29. Shinnick TM, Lerner RA, Sutcliffe JG (1981) Nucleotide sequence of Moloney murine leukemia virus. Nature 293: 543–548PubMedCrossRefGoogle Scholar
  30. Valle RPC, Morch M-D, Haenni AL (1987) Novel amber suppressor tRNAs of mammalian origin. EMBO J 6: 3049–3055PubMedGoogle Scholar
  31. Weiss WA, Friedberg EC (1986) Normal yeast tRNAc’gc can suppress amber codons and is encoded by an essential gene. J Mol Biol 192: 725–735PubMedCrossRefGoogle Scholar
  32. Yamao F, Muto A, Kawauchi Y, Iwami M, Iwagami S, Azumi Y, Osawa S (1985) UGA is readas tryptophan in Mycoplasma capricolum. Proc Natl Acad Sci USA 82: 2306–2309PubMedCrossRefGoogle Scholar
  33. Yang JA, Tai LW, Agris PF, Gehrke CW, Wong TW (1983) The nucleotide sequence of a major glutamine tRNA from rat liver. Nucleic Acids Res 11: 1991–1996PubMedCrossRefGoogle Scholar
  34. Yoshinaka Y, Katoh I, Copeland TD, Oroszlan S (1985) Murine leukemia virus protease is encoded by the gag-pol gene and is synthesized through suppression of an amber termination codon. Proc Natl Acad Sci USA 82: 1618–1622PubMedCrossRefGoogle Scholar
  35. Zinoni F, Birkmann A, Stadtman TC, Böck A (1986) Nucleotide sequence and expression of the selenocysteine-containing polypeptide of formate dehydrogenase (formate-hydrogenlyaselinked) from Escherichia coli. Proc Natl Acad Sci USA 83: 4650–4654PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • Y. Kuchino
    • 1
  • S. Nishimura
    • 2
  • H. C. Schröder
    • 3
  • W. E. G. Müller
    • 3
  1. 1.Biophysics DivisionNational Cancer Center Research InstituteChuo-ku, Tokyo 104Japan
  2. 2.Biology DivisionNational Cancer Center Research InstituteChuo-ku, Tokyo 104Japan
  3. 3.Abt. Angewandte MolekularbiologieInstitut für Physiologische ChemieMainzGermany

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