Functional Aspects of Three Modified Nucleosides, Ψ, ms2io6A, and m1G, Present in the Anticodon Loop of tRNA

  • Tord G. Hagervall
  • Birgitta Esberg
  • Ji-nong Li
  • Thérèse M. F. Tuohy
  • John F. Atkins
  • James F. Curran
  • Glenn R. Björk


Transfer RNAs contain many modified nucleosides, which are derivatives of the four normal nucleosides. At present more than 75 different modified nucleosides are characterised (Edmonds et al., 1991). The synthesis of the majority of the modified nucleosides is carried out on the preformed precursor tRNA except in two cases. Queuine and hypoxanthine are synthesised from guanine and adenine, respectively, and then incorporated into the tRNA through an exchange reaction. The synthesis of these 75 modified nucleosides is catalysed by enzymes, which are highly specific, not only for the nucleoside that they modify but also for the position of the target nucleoside in the tRNA. For example there are different enzymes catalysing the formation of Ψ in the anticodon stem and in the TΨC-loop (Singer et al., 1972). The importance of tRNA modification is reflected by the fact that about 1% of the genetic information in Escherichia coli and Salmonella typhimurium is devoted to the synthesis of tRNA modifying enzymes, which is 4-fold more than that used for the synthesis of their substrate, tRNA (Björk, 1992). This paper will discuss the function of three modified nucleosides present in the anticodon region. Mutants defective in their synthesis have been used to study their role in cell physiology and in the decoding process.


Anticodon Loop Modify Nucleoside Sense Codon Codon Context tRNA Modification 
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  1. Avis, P.F., Armstrong, D. J., Schäfer, K. P., and Söll, D. (1975). Maturation of ahypermodified nucleoside in transfer RNA. Nucl. Acids Res. 2: 691–698.CrossRefGoogle Scholar
  2. W.M. Barnes 1978 region: seven histidine codons in a row. Proc. Natl. Acad. Sci.(USA), 75: 42–81Google Scholar
  3. Björk, G. R. (1984). Transfer RNA modification in different organisms. Chemica Scripta. 26B: 91–95.Google Scholar
  4. Björk G. R. (1992). The role of modified nucleosides in transfer RNA interactions. in: “Transfer RNA in protein synthesis”. Hatfield, D. L., Lee, B. J., and, Pirtle R. M., eds, CRC press, Boca Raton, FL.Google Scholar
  5. Björk, G. R., Wikström, P. M., and Byström, A. S. (1989). Prevention of translational frameshifting by the modified nucleoside 1-Methylguanosine. Science 244: 986–989.Google Scholar
  6. Bossi, L., and Roth, J. R.. (1980). The influence of codon context on genetic code translation. Nature 286:123–127.PubMedCrossRefGoogle Scholar
  7. Bouadloun, F, Srichaiyo, T., Isaksson L. A., and Björk G. R. (1986). Influence of modification next to the anticodon in tRNA on codon context sensitivity of translational suppression and accuracy. J. Bacteriol. 166: 1022–1027.PubMedGoogle Scholar
  8. Buck M., and Ames B. N. (1984). A modified nucleotide in tRNA as a possible regulator of aerobiosis: Synthesis of cis-2-methyl-thioribosylzeatin in tRNA of Salmonella. Cell 36: 523–531.Google Scholar
  9. Buck, M., McCloskey, J. A., Basile, B., and Ames, B. N. (1982). Cis-2-methylthioribosylzeatin (ms2io6A) is present in transfer RNA of Salmonella typhimurium, but not Escherichia coll. Nucl. Acids Res. 10: 5649–5662.Google Scholar
  10. Byström, A. S., Hjalmarsson, K. J., Wikström, P. M., and Björk, G. R. (1983). The nucleotide sequence of an Escherichia coli operon containing genes for the tRNA(m1G)methyltransferase, the ribosomal proteins S16 and L19 and a 21-K polypeptide. EMBO J. 2: 899–905.PubMedGoogle Scholar
  11. Carter, P. W., Weiss, D. L., Weith, H. L., and Calvo J. M. (1985). Mutations that convert the four leucine codons of the Salmonella typhimurium leu leader to four threonine codons. J. Bacteriol. 162: 943–949.PubMedGoogle Scholar
  12. Connolly, D. M., and Winkler, M.E. (1991). Structure of Escherichia coli K-12 miaA and characterization of the mutator phenotype caused by miaA insertion mutations. J. Bacteriol. 173: 1711–1721.PubMedGoogle Scholar
  13. Cortese, R., Kammen, H. O., Spengler, S. J., and Ames B. N. (1974).Biosynthesis ofpseudouridine in transfer ribonucleic acid. J. Biol. Chem. 249: 1103–1108.PubMedGoogle Scholar
  14. Craigen, W. J., Cook, R. G., Tate, W. P., and Caskey, C. T. (1985). Proc. Natl. Acad. Sci.USA 82: 3616–3620.PubMedCrossRefGoogle Scholar
  15. Curran, J. F., and Yarus, M. (1987). Reading frame selection and transfer RNA anticodon loop stacking. Science 238: 1545–1550.PubMedCrossRefGoogle Scholar
  16. Curran, J. F., and Yarus, M. (1988). Use of tRNA suppressors to probe the regulation of Escherichia coli release factor 2. J. Mol. Biol. 203: 75–83.PubMedCrossRefGoogle Scholar
  17. Curran, J. F., and Yarus, M. 1989. Rates of aminoacyl-tRNA selection at 29 sense codons in vivo. J. Mol. Biol. 209: 65–77.Google Scholar
  18. Diaz, I., and Ehrenberg, M. (1992). ms2i6A deficiency enhances proofreading in translation. J. Mol. Biol. 222: 1161–1171.CrossRefGoogle Scholar
  19. Edmonds, C. G., Crain, P. F., Gupta, R., Hashizume, T., Hocart, C. H., Kowalak, J. A., Pomerantz, S. C.,. Stetter K. O, and McCloskey, J. A..(1991). Posttranscriptional modification of tRNA in thermophilic Archaea (Archaebacteria). J Bacteriol. 173: 3138–3148.PubMedGoogle Scholar
  20. Eisenberg, S. P., Yarus, M., and, Soll, L. 1979. The effect of an Escherichia coil regulatory mutation on transfer RNA structure. J. Mol. Biol. 135: 111–126.PubMedCrossRefGoogle Scholar
  21. Ericson, J. U., and Björk, G. R. 1986. Pleiotropic effects induced by modification deficiency next to the anticodon of tRNA from Salmonella typhimurium LT2. J. Bacteriol. 166: 1013–1021.PubMedGoogle Scholar
  22. Ericson, J. U., and Björk, G. R. (1991). tRNA anticodons with the modified nucleoside 2methylthio-N6-(4-hydroxyisopentenyl)adenosine distinguish between bases 3’ of the codon. J Mol. Biol. 218: 509–516.PubMedCrossRefGoogle Scholar
  23. Gaber R. F. and, Culbertson M. R. (1984). Codon recognition during frameshift suppression in Saccharomyces cerevisiae. Mol.Cell.Biol 4: 2052–2061.Google Scholar
  24. Griffiths, E., and, Humphreys, J. 1978. Alterations in tRNAs containing 2-methylthio-N6-A 2-isopentenyl)-adenosine during growth of enteropathogenic Escherichia coli in the presence of iron-binding proteins. Eur. J. Biochem. 82: 503–513.PubMedCrossRefGoogle Scholar
  25. Grosjean, H., K. Nicoghosian, K., Haumont, E., Söll, D. and, Cedergren, R. 1985. Nucleotide sequences of two serine tRNAs with a GGA anticodon: The structure-function relationships in the serine family of E. coli tRNAs. Nucl. Acid Res. 13: 5697–5706.CrossRefGoogle Scholar
  26. Hagervall, T. G., Tuohy, T. M. F., Atkins J. F. and, Björk, G. R. (1992). Deficiency of 1methylguanosine in tRNA from Salmonella typhimurium induces frameshifting by quadruplet translocation. J. Mol Biol. Submitted.Google Scholar
  27. Hagervall, T. G., Ericson, J. U., Esberg, K. B., Ji-nong, L. and, Björk, G. R. 1990. Role tRNA modification in translation fidelity. Biochem. Biophys. Acta 1050: 263–266.CrossRefGoogle Scholar
  28. Hall, R. H. The modified nucleosides in nucleic acids. Columbia University Press. 1971. Johnston, H. M., Barnes, W. M., Chumley, F. G., Bossi, L., and Roth, J. R. Model for regulation of the histidine operon of Salmonella. Proc. Natl. Acad. Sci. (USA). 77: 508, 1980.Google Scholar
  29. Komine Y., Adachi T., Inokuchi H., Ozeki H. (1990). Genomic organization and physical mapping of the transfer RNA genes in Escherichia coli K12. J. Mol. Biol. 212: 579–598.PubMedCrossRefGoogle Scholar
  30. Newmark R. A. & Cantor C. R. (1968). Nuclear magnetic resonance study of the interactions of guanosine and cytidine in dimethyl sulfoxide. J. Am. Chem. Soc. 90: 5010–5017.PubMedCrossRefGoogle Scholar
  31. Palmer, D. T., P. H. Blum, and S. W. Artz,1983. Effects of the hisT mutation of Salmonella typhimurium on translation elongation rate. J. Bacteriol. 153: 357–363.PubMedGoogle Scholar
  32. Parker, J. 1982. Specific mistranslation in hisT mutants of Escherichia coli Mol Gen. Genet. 187: 405–409.Google Scholar
  33. Pieczenik G. (1980). Predicting coding function from nucleotide sequence or survival of “fitness” of tRNA. Proc. Natl. Acad. Sci. USA. 77: 3539–3543.PubMedCrossRefGoogle Scholar
  34. Rosenberg, A. H., and M. L. Gefter. 1969. An iron-dependent modification of several transfer RNA species in Escherichia coll. J. Mol. Biol. 46: 581–584.Google Scholar
  35. Roth, J. R, D. N. Anton, and P. E. Hartman. 1966. Histidine regulatory mutants in Salmonella typhimurium. I. Isolation and general properties.J. Mol. Biol. 22: 305–323.PubMedCrossRefGoogle Scholar
  36. Singer, C., Smith G. R., Cortese C., and Ames B. N. (1972). Mutant tRNA ineffective in repression and lacking two pseudouridine modifications. Nature (London) New Biol. 238: 72.Google Scholar
  37. Sprinzl M., Dank N., Nock S., Schön A. (1991). Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res. 19: supplement, 2127–2171.PubMedCrossRefGoogle Scholar
  38. Sroga G. E., Nemoto F., Kuchino Y. and, Björk G. R. (1992). Insertion in the anticodon loop or base substitution (sufC) in the anticodon stem of tRNA PZ from Salmonella typhimurium induces suppression of frameshift mutations. Nucl. Acids. Res. 20:3463–3469.PubMedCrossRefGoogle Scholar
  39. Turnbough Jr., C. L., Neill, R. J., Landsberg, R. and, Ames, B. N. (1979). Pseudouridylation of tRNAs and its role in regulation in Salmonella typhimurium. J. Biol. Chem. 254: 5111–5119.PubMedGoogle Scholar
  40. Weiss R. B:, Dunn D. M., Atkins J. F., Gesteland R. F. (1987). Slippery runs, shifty stops, backward steps and forward hops: -2, -1, +1, +2, +5, and +6 ribosomal frameshifting. Cold Spring Harbor Symp. Quant. Biol. 52: 687–693.PubMedCrossRefGoogle Scholar
  41. Weiss, R. B., D. M. Dunn, J. E. Dahlberg, J. F. Atkins, and R. F. Gesteland. 1988. EMBO J. 7:1503–1507.PubMedGoogle Scholar
  42. Weiss R. B., Dunn D. M., Atkins J. F., Gesteland R. F. (1990). Ribosomal frameshifting from -2 to +50 nucleotides. Prog Nucl Acid Mol Biol 39: 159–183.CrossRefGoogle Scholar
  43. Wettstein, F. O., and G. S. Stent. 1968. Physiologically induced changes in the property of phenylalanine tRNA in Escherichia coli. J. Mol. Biol. 38: 25–40.Google Scholar
  44. Woese, C. R. 1967. in: “The genetic code. The molecular basis for genetic expression”. Harper and Row, p. 134.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Tord G. Hagervall
    • 1
  • Birgitta Esberg
    • 1
  • Ji-nong Li
    • 1
  • Thérèse M. F. Tuohy
    • 2
  • John F. Atkins
    • 2
  • James F. Curran
    • 3
  • Glenn R. Björk
    • 1
  1. 1.Department of MicrobiologyUniversity of UmeåUmeåSweden
  2. 2.Howard Hughes Medical Institute and Department of Human GeneticsUniversity of UtahSalt Lake CityUSA
  3. 3.Department of BiologyWake Forest UnivesityWinston-SalemUSA

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