Codon Context, Translational Step-Times and Attenuation

  • G. W. Hatfield


Charles Yanofsky and his co-workers have provided us with a detailed understanding of the attenuation mechanism for the regulation of the tryptophan operon of Escherichia coli. This understanding is based on the results of rigorous experimental documentation gathered over the course of the last 15 years. During this time, attenuation mechanisms have also been elucidated for several other operons required for the biosynthesis of amino acids and intermediary metabolites in bacteria. Most recently, Yanofsky and his co-workers have described a model for setting the basal level of transcriptional readthrough at the attenuator of the trp operon. This model, which is supported by a great deal of experimental evidence and has been reviewed elsewhere,1–3 emphasizes the importance of the timing and synchronization of the movement of an RNA polymerase and a ribosome through the leader-attenuator region, i.e., the mechanistic importance of the relative transcription and translation elongation rates for attenuation. While much has been learned about the transit of an RNA polymerase molecule through the leader-attenuator region of the trp operon, little is known about the mechanisms that influence the movement of the ribosome. Indeed, little is known about the mechanisms that influence elongation rates and pausing during the translation of any messenger RNA.


Codon Usage Codon Pair Attenuation Mechanism Codon Context Tryptophan Operon 
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  1. 1.
    Landick R, Yanofsky C. Transcription attenuation. In: Neidheidhardt FC, Ingraham JL, Low KB, Magasanik B, Schaechter M, Umbarger HE, eds. Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. Washington, D.C.: American Society for Microbiology, 1987:1276–1301.Google Scholar
  2. 2.
    Landick R, Turnbough CL. Transcriptional attenuation. In: McKnight SL, Yamamoto K, ed. Transcriptional Regulation. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1992:407–446.Google Scholar
  3. 3.
    Hatfield GW. A two ribosome model for attenuation. In: Ilan J, ed. Translational expression of gene expression 2. New York, NY: Plenum Publishing Corporation, 1993:1–22.CrossRefGoogle Scholar
  4. 4.
    Hatfield GW, Gutman GA. Codon pair utilization bias in bacteria, yeast and mammals. In: Hatfield DL, Lee BJ, Pirtle RM, ed. Transfer RNA in Protein Synthesis. Boca Raton, LA: CRC Press, 1993:157–189.Google Scholar
  5. 5.
    Gutman GA, Hatfield GW. Nonrandom utilization of codon pairs in Escherichia coli. Proc Natl Acad Sci USA 1989; 86(10):3699–703.CrossRefGoogle Scholar
  6. 6.
    Aloni Y, Hay N. Attenuation may regulate gene expression in animal viruses and cells. CRC Crit Rev Biochem 1985; 18(4):327–83.CrossRefGoogle Scholar
  7. 7.
    Yanofsky C. Transcription attenuation. J Biol Chem 1988; 263(2):609–12.Google Scholar
  8. 8.
    Bertrand K, Korn LJ, Lee F, Yanofsky C. The attenuator of the tryptophan Operon of Escherichia coli. Heterogeneous 3′-OH termini in vivo and deletion mapping of functions. J Mol Biol 1977; 117(1):227–47.CrossRefGoogle Scholar
  9. 9.
    Bertrand K, Squires C, Yanofsky C. Transcription termination in vivo in the leader region of the tryptophan Operon of Escherichia coli. J Mol Biol 1976; 103(2):319–37.CrossRefGoogle Scholar
  10. 10.
    Bertrand K, Yanofsky C. Regulation of transcription termination in the leader region of the tryptophan Operon of Escherichia coli involves tryptophan or its metabolic product. J Mol Biol 1976; 103(2):339–49.CrossRefGoogle Scholar
  11. 11.
    Lee F, Squires CL, Squires C, Yanofsky C. Termination of transcription in vitro in the Escherichia coli tryptophan Operon leader region. J Mol Biol 1976; 103(2):383–93.CrossRefGoogle Scholar
  12. 12.
    Friden P, Newman T, Freundlich M. Nucleotide sequence of the ilvB promoter-regulatory region: a biosynthetic operon controlled by attenuation and cyclic AMP. Proc Natl Acad Sci USA 1982; 79(20):6156–60.CrossRefGoogle Scholar
  13. 13.
    Hauser CA, Hatfield GW. Nucleotide sequence of the ilvB multivalent attenuator region of Escherichia coli K12. Nucleic Acids Res 1983; ll(l):127–39.CrossRefGoogle Scholar
  14. 14.
    Lawther RP, Hatfield GW. Multivalent translational control of transcription termination at attenuator of ilvGEDA operon of Escherichia coli K-12. Proc Natl Acad Sci USA 1980; 77(4): 1862–6.CrossRefGoogle Scholar
  15. 15.
    Nargang FE, Subrahmanyam CS, Umbarger HE. Nucleotide sequence of ilvGEDA operon attenuator region of Escherichia coli. Proc Natl Acad Sci USA 1980; 77(4):1823–7.CrossRefGoogle Scholar
  16. 16.
    Gardner JF. Regulation of the threonine operon: tandem threonine and isoleucine codons in the control region and translational control of transcription termination. Proc Natl Acad Sci USA 1979; 76(4): 1706–10.CrossRefGoogle Scholar
  17. 17.
    Gemmill RM, Sessler SR, Calvo JM. leu operon of Salmonnella typhimurium is controlled by attenuation. Proc Natl Acad Sci USA 1979; 76:4941–4945.CrossRefGoogle Scholar
  18. 18.
    Barnes WM. DNA sequence from the histidine control region: seven histidine codons in a row. Proc Natl Acad Sci USA 1978; 75(4281–4285).CrossRefGoogle Scholar
  19. 19.
    DiNocera PP, Blasi F, DiLauro R, Frunzio R, Bruni CB. Nucleotide sequence of the attenuator region of the histidine operon of Escherichia coli K-12. Proc Natl Acad Sci USA 1978; 75:4276–4280.CrossRefGoogle Scholar
  20. 20.
    Zurawski G, Brown K, Killingly D, Yanofsky C. Nucleotide sequence of the leader region of the phenylalanine operon of Escherichia coli. Proc Natl Acad Sci USA 1978; 75(9):4271–5.CrossRefGoogle Scholar
  21. 21.
    Curran JF, Yarus M. Use of tRNA suppressors to probe regulation of Escherichia coli release factor 2. J Mol Biol 1988; 203(1):75–83.CrossRefGoogle Scholar
  22. 22.
    Gausing K. Efficiency of protein and messenger RNA synthesis in bacteriophage T4-infected cells of Escherichia coli. J Mol Biol 1972; 71(3):529–45.CrossRefGoogle Scholar
  23. 23.
    Roesser JR, Nakamura Y, Yanofsky C. Regulation of basal level expression of the tryptophan operon of Escherichia coli. J Biol Chem 1989; 264(21):12284–8.Google Scholar
  24. 24.
    Roesser JR, Yanofsky C. Ribosome release modulates basal level expression of the trp operon of Escherichia coli. J Biol Chem 1988; 263(28): 14251–5.Google Scholar
  25. 25.
    Caskey CT. Peptide chain termination. Trends Biochem Sci 1980; 54:234–237.CrossRefGoogle Scholar
  26. 26.
    Suzuki H, Kunisawa T, Otsuka J. Theoretical evaluation of transcriptional pausing effect on the attenuation of trp leader sequence. Biophys J 1986; 49:425–436.CrossRefGoogle Scholar
  27. 27.
    Steitz JA. RNA-RNA interactions in ribosome translation initiation. In: Chambliss G, Craven GR, Davies J, Davis K, Kahan L, Nomura M, eds. Ribosomes: Structure Function and Genetics. Baltimore: University Park Press, 1980:479–495.Google Scholar
  28. 28.
    Protzel A, Morris AJ. Gel chromatographic analysis of nascent globin chains. Evidence of nonuniform size distribution. J Biol Chem 1974; 249:4594.Google Scholar
  29. 29.
    Lizardi PM, Mahdari V, Shields D, Candelas G. Discontinuous translation of silk fibroin in a reticulocyte cell-free system and in intact silk gland cells. Proc Natl Acad Sci USA 1979; 76:6211.CrossRefGoogle Scholar
  30. 30.
    Candelas G, Candelas T, Ortiz A, Rodriguez O. Translational pauses during a spider fibroin synthesis. Biochem Biophys Res Commun 1983; 116:1033.CrossRefGoogle Scholar
  31. 31.
    Varenne S, Knibiehler M, Cavard D, Morion J, Lazdunski C. Variable rate of polypeptide elongation for colicins A, E2, and E3. J Mol Biol 1982; 159:57.CrossRefGoogle Scholar
  32. 32.
    Chaney W, Morris A. Nonuniform size distribution of nascent peptides. The effect of messenger RNA structure upon the rate of translation. Arch Biochem Biophys 1979; 194:283.CrossRefGoogle Scholar
  33. 33.
    Randall LL, Josefsson LG, Hardy SJS. Novel intermediates in the synthesis of maltose-binding protein in Escherichia coli. Eur J Biochem 1980; 107:375.CrossRefGoogle Scholar
  34. 34.
    Abraham AK, Pihl A. Variable rate of polypeptide chain elongation in vitro. Eur J Biochem 1980; 106:257.CrossRefGoogle Scholar
  35. 35.
    Wolin SL, Walter P. Ribosome pausing and stacking during translation of a eukaryotic mRNA. Embo J 1988; 7(11):3559–69.Google Scholar
  36. 36.
    Gouy M, Gautier C. Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Res 1982; 10:7055–61.CrossRefGoogle Scholar
  37. 37.
    Liljenstrom H, von Heinje G. Translation rate modification by preferential codon usage. J Theor Biol 1987; 124:43–8.CrossRefGoogle Scholar
  38. 38.
    Kuroda MI, Yanofsky C. Evidence for the transcript secondary structures predicted to regulate transcription attenuation in the trp Operon. J Biol Chem 1984; 259(20):12838–43.Google Scholar
  39. 39.
    Oxender DL, Zurawski G, Yanofsky C. Attenuation in the Escherichia coli tryptophan Operon: role of RNA secondary structure involving the tryptophan codon region. Proc Natl Acad Sci USA 1979; 76(11):5524–8.CrossRefGoogle Scholar
  40. 40.
    Kolter R, Yanofsky C. Genetic analysis of the tryptophan operon regulatory region using site-directed mutagenesis. J Mol Biol 1984; 175(3): 299–312.CrossRefGoogle Scholar
  41. 41.
    Landick R, Yanofsky C, Choo K, Phung L. Replacement of the Escherichia coli trp operon attenuation control codons alters operon expression. J Mol Biol 1990; 216(1):25–37.CrossRefGoogle Scholar
  42. 42.
    Bonekamp F, Dalbege H, Christensen T, Jensen KF. Translation rates of individual codons are not correlated with tRNA abundances or with frequencies of utilization in Escherichia coli. J Bact 1989; 171(11):5812–5816.Google Scholar
  43. 43.
    Robinson M, Lilley R, Little S et al. Codon usage can affect efficiency of translation of genes in Escherichia coli. Nucleic Acids Res 1984; 12:6663.CrossRefGoogle Scholar
  44. 44.
    . Lynn SP, Burton WS, Donohue TJ, Gould RM, Gumport RI, Gardner JF. Specificity of the attenuation response of the threonine operon of Escherichia coli is determined by the threonine and isoleucine codons in the leader transcript. J Mol Biol 1987; 194(l):59–69.CrossRefGoogle Scholar
  45. 45.
    Chen JW, Bennett DC, Umbarger HE. Specificity of attenuation control in the ilvGMEDA operon of Escherichia coli K-12 [published erratum appears in J Bacteriol 1991 May; 173(10):3269]. J Bacteriol 1991; 173(7):2328–40.Google Scholar
  46. 46.
    . Chen JW, Harms E, Umbarger HE. Mutations replacing the leucine codons or altering the length of the amino acid-coding portion of the ilvGMEDA leader region of Escherichia coli. J Bacteriol 1991; 173(7): 2341–53.Google Scholar
  47. 47.
    . Carter PW, Weiss DL, Weith HL, Calvo JM. Mutations that convert the four leucine codons of the Salmonella typhimurium leu leader to four threonine codons. J Bacteriol 1985; 162(3):943–9.Google Scholar
  48. 48.
    Irwin B, Heck JD, Hatfield GW. Codon pair utilization biases influence translational elongation step times. J Biol Chem 1995; 270(39):22801–6.CrossRefGoogle Scholar

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© R.G. Landes Company 1996

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  • G. W. Hatfield

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