Molecular Biology

, 40:440 | Cite as

Model of gene expression regulation in bacteria via formation of RNA secondary structures

  • V. A. Lyubetsky
  • L. I. Rubanov
  • A. V. Seliverstov
  • S. A. Pirogov
Mathematical and System Biology


A model was proposed for the classical attenuating mRNA regulation of gene expression via transcription termination. The model is based on the concept of secondary structure macrostates in the RNA regulatory region between the ribosome and RNA polymerase, utilizes resonant equations for estimating the deceleration of RNA polymerase by a set of hairpins located in this RNA region, and takes into account views on the initiation and elongation of transcription and translation. Special attention was paid to selecting the model parameters. To test the model, computations were performed to estimate, in particular, the probability of translation termination as dependent on the charged tRNA concentration and the amino acid concentration for several regulatory regions of the bacterial genome (as exemplified by trpE of Streptomyces spp., Bradyrhizobium japonicum, and Escherichia coli). Analysis was performed with different values of three parameters isolated as major ones. The resulting dependences agreed with the available experimental data, including those characterizing an enzymatic activity as dependent on the amino acid concentration in a culture (e.g., the anthranylate synthase activity as dependent on the tryptophan concentration in S. venezuelae). The following possible application was proposed for the model. Attenuating regulation is usually predicted on the basis of multiple sequence alignment, which requires several sequences. With the model, an individual sequence can be analyzed with proper parameters to generate a concentration-enzymatic activity curve. The curve characteristic of attenuation or its absence provides an additional argument for the presence or absence of attenuation.

Key words

attenuation model of transcriptional regulation mathematical model in genetics 


  1. 1.
    Henkin T.M., Yanofsky C. 2002. Regulation by transcription attenuation in bacteria: How RNA provides instructions for transcription termination/antitermination decisions. Bioessays. 24, 700–707.PubMedCrossRefGoogle Scholar
  2. 2.
    Grundy F.J., Henkin T.M. 2003. The T box and S box transcription termination control systems. Front. Biosci. 8, 20–31.Google Scholar
  3. 3.
    Grundy F.J., Henkin T.M. 2004. Regulation of gene expression by effectors that bind to RNA. Curr. Opin. Microbiol. 7(2), 126–131.PubMedCrossRefGoogle Scholar
  4. 4.
    Mandal M., Breaker R.R. 2004. Gene regulation by riboswitches. Nature Rev. Mol. Cell. Biol. 5, 451–463.CrossRefGoogle Scholar
  5. 5.
    Vitreschak A.G., Rodionov D.A., Mironov A.A., Gelfand M.S. 2004. Riboswitches: The oldest mechanism for the regulation of gene expression? Trends Genet. 20, 44–50.PubMedCrossRefGoogle Scholar
  6. 6.
    Yanofsky C. 2004. The different roles of tryptophan transfer RNA in regulating trp operon expression in E. coli versus B. subtilis. Trends Genetics. 20(8), 367–374.CrossRefGoogle Scholar
  7. 7.
    Panina E.M., Vitreschak A.G., Mironov A.A., Gelfand M.S. 2001. Regulation of aromatic amino acid biosynthesis in gamma-proteobacteria. J. Mol. Microbiol. Biotechnol. 3, 529–543.PubMedGoogle Scholar
  8. 8.
    Vitreschak A.G., Lyubetskaya E.V., Shirshin M.A., Gelfand M.S., Lyubetsky V.A. 2004. Attenuation regulation of amino acid biosynthetic operons in proteobacteria: Comparative genomics analysis. FEMS Microbiol. Lett. 234, 357–370.PubMedGoogle Scholar
  9. 9.
    Grundy F.J., Henkin T.M. 1994. Conservation of a transcription antitermination mechanism in aminoacyl-tRNA synthetase and amino acid biosynthesis genes in Gram-positive bacteria. J. Mol. Biol. 235, 798–804.PubMedCrossRefGoogle Scholar
  10. 10.
    Grundy F.J., Henkin T.M. 1998. The S box regulon: A new global transcription termination control system for methionine and cysteine biosynthesis genes in Gram-positive bacteria. Mol. Microbiol. 30, 737–749.PubMedCrossRefGoogle Scholar
  11. 11.
    Murphy B.A., Grundy F.J., Henkin T.M. 2002. Prediction of gene function in methylthioadenosine recycling from regulatory signals. J. Bacteriol. 184, 2314–2318.PubMedCrossRefGoogle Scholar
  12. 12.
    Panina E.M., Vitreschak A.G., Mironov A.A., Gelfand M.S. 2003. Regulation of biosynthesis and transport of aromatic amino acid in low-GC Gram-positive bacteria. FEMS Microbiol. Letts. 222, 211–220.CrossRefGoogle Scholar
  13. 13.
    Sudarsan N., Barrick J.E., Breaker R.R. 2003. Metabolite-binding RNA domains are present in the genes of eukaryotes. RNA. 9, 644–647.PubMedCrossRefGoogle Scholar
  14. 14.
    Rodionov D.A., Vitreschak A.A., Mironov A.A., Gelfand M.S. 2003. Computational analysis of thiamin regulation in bacteria: Possible mechanisms and new THI-element-regulated genes. J. Biol. Chem. 277, 48949–48959.CrossRefGoogle Scholar
  15. 15.
    Henkin T.M., Glass B.L., Grundy F.J. 1992. Analysis of the Bacillus subtilis tyrS gene: Conservation of a regulatory sequence in multiple tRNA synthetase genes. J. Bacteriol. 174, 1299–1306.PubMedGoogle Scholar
  16. 16.
    Seliverstov A.V., Putzer H., Gelfand M.S., Lyubetsky V.A. 2005. Comparative analysis of RNA regulatory elements of amino acid metabolism genes in Actinobacteria. BMC Microbiology. 5, 54.PubMedCrossRefGoogle Scholar
  17. 17.
    Barrick J.E., Corbino K.A., Winkler W.C., Nahvi A., Mandal M., Collins J., Lee M., Roth A., Sudarsan N., Jona I., Wickiser J.K., Breaker R.R. 2004. New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control. Proc. Natl. Acad. Sci. USA. 101, 6421–6426.PubMedCrossRefGoogle Scholar
  18. 18.
    Abreu-Goodger C., Ontiveros-Palacios N., Ciria R., Merino E. 2004. Conserved regulatory motifs in bacteria: Riboswitches and beyond. Trends Genet. 20(10), 475–479.PubMedCrossRefGoogle Scholar
  19. 19.
    Vitreschak A.A., Rodionov D.A., Mironov A.A., Gelfand M.S. 2002. Regulation of riboflavin biosynthesis and transport genes in bacteria by transcriptional and translational attenuation. Nucleic Acids Res. 30, 3141–3151.PubMedCrossRefGoogle Scholar
  20. 20.
    Vitreschak A.G., Rodionov D.A., Mironov A.A., Gelfand M.S. 2003. Regulation of the vitamin B12 metabolism and transport in bacteria by a conserved RNA structural element. RNA. 9, 1084–1097.PubMedCrossRefGoogle Scholar
  21. 21.
    Singer M., Berg P. 1998. Genes and Genomes. Moscow: Mir.Google Scholar
  22. 22.
    Mironov A.A., Kister A.E. 1985. Theoretical analysis of secondary RNA structure formation kinetics in the course of transcription and translation: Account of defective helices. Mol. Biol. 19, 1350–1357.Google Scholar
  23. 23.
    Mironov A.A., Kister A.E. 1989. Theoretical analysis of structural rearrangements in the course of secondary RNA structure formation. Mol. Biol. 23, 61–71.Google Scholar
  24. 24.
    Mironov A.A., Lebedev V.F. 1993. A kinetic model of RNA folding. BioSystems. 30, 49–56.PubMedCrossRefGoogle Scholar
  25. 25.
    Elf J., Ehrenberg M. 2005. What makes ribosome-mediated transcriptional attenuation sensitive to amino acid limitation? PLoS Comput. Biology. 1(1), e2.Google Scholar
  26. 26.
    Xayaphoummine A., Bucher T., Thalmann F., Isambert H. 2003. Prediction and statistics of pseudoknots in RNA structures using exactly clustered stochastic simulations. Proc. Natl. Acad. Sci. USA. 100, 15310–15315.PubMedCrossRefGoogle Scholar
  27. 27.
    Xayaphoummine A., Bucher T., Isambert H. 2005. Kinefold web server for RNA/DNA folding path and structure prediction including pseudoknots and knots. Nucleic Acids Res. 33 (Web Server issue), W605-10.Google Scholar
  28. 28.
    Pirogov S.A., Gorbunov K.Yu., Lyubetsky V.A. 2005. Macro-and microstates in the attentuation model of gene expression regulation in bacteria. Trudy 7 Mezhd. Konf. “Problemy upravleniya i modelirovaniya v slozhnykh sistemakh” (Proc. 7th Int. Conf. “Problems of Control and Modeling in Complex Systems”), Samara: Ross. Akad. Nauk, 210–216.Google Scholar
  29. 29.
    Lyubetsky V.A., Pirogov S.A. 2005. The model of attenuation regulation in bacteria. Trudy 7 Mezhd. Konf. “Problemy upravleniya i modelirovaniya v slozhnykh sistemakh” (Proc. 7th Int. Conf. “Problems of Control and Modeling in Complex Systems”), Samara: Ross. Akad. Nauk, 205–210.Google Scholar
  30. 30.
    Mathews D.H., Sabina J., Zuker M., Turner D.H. 1999. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J. Mol. Biol. 288, 911–940.PubMedCrossRefGoogle Scholar
  31. 31.
    Mathews D.H., Disney M.D., Childs J.L., Schroeder S.J., Zuker M., Turner D.H. 2004. Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc. Natl. Acad. Sci. USA. 101, 7287–7292.PubMedCrossRefGoogle Scholar
  32. 32.
    Dima I., Hyeon C., Thirumalai D. 2005. Extracting stacking interaction parameters for RNA from the data set of native structures. J. Mol. Biol. 347, 53–69.PubMedCrossRefGoogle Scholar
  33. 33.
    RNA Structure, Turner Lab,
  34. 34.
    Lawler G.F., Coyle L.N. 1999. Lectures on Contemporary Probability, AMS.Google Scholar
  35. 35.
    Yin H., Artsimovitch I., Landick R., Gelles J. 1999. Non-equilibrium mechanism of translation termination from observations of single RNA polymerase molecules. Proc. Natl. Acad. Sci. USA. 96, 13124–13129.PubMedCrossRefGoogle Scholar
  36. 36.
    Wilson K., von Hippel P. 1995. Transcription termination at intrinsic terminators: The role of the RNA hairpin. Proc. Natl. Acad. Sci. USA. 92, 8793–8797.PubMedCrossRefGoogle Scholar
  37. 37.
    Lynn S., Kasper L., Gardner J. 1988. Contributions of RNA secondary structure and length of the thymidine tract to transcription termination at the thr operon attenuator. J. Biol. Chem. 263, 472–479.PubMedGoogle Scholar
  38. 38.
    Lin Cong, Paradkar A.S., Vining L.C. 1998. Regulation of an anthranilate synthase gene in Streptomyces venezuelae by a trp attenuator. Microbiology. 144, 1971–1980.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2006

Authors and Affiliations

  • V. A. Lyubetsky
    • 1
  • L. I. Rubanov
    • 1
  • A. V. Seliverstov
    • 1
  • S. A. Pirogov
    • 1
  1. 1.Institute of Information Transmission ProblemsRussian Academy of SciencesMoscowRussia

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