Several species of the genus are human pathogens, notably the tubercle bacillus (). The rate of proliferation of a bacterium is reflected in the rate of ribosome synthesis. This report describes a quantitative analysis of the early stages of the synthesis of ribosomes of . Specifically, the roles of three large operons, namely: the operon (1.7 microns) encoding (16S rRNA), (23S rRNA) and (5S rRNA); the operon (1.93 microns), which encodes 11 ribosomal proteins; and the operon (1.45 microns), which encodes 10 ribosomal proteins. A mathematical framework based on properties of population-average cells was developed to identify the number of transcripts of the and operons needed to maintain exponential growth. The values obtained were supported by RNaseq data. The motif 5′-gcagac-3′ was found close to 5′ end of transcripts of mycobacterial operons, suggesting it may form part of the RpsH feedback binding site because the same motif is present in the ribosome within the region of that forms the binding site for RpsH.


Article metrics loading...

Loading full text...

Full text loading...



  1. Arnvig K. B., Comas I., Thomson N. R., Houghton J., Boshoff H. I., Croucher N. J., Rose G., Perkins T. T., Parkhill J. et al.(2011). Sequence-based analysis uncovers an abundance of non-coding RNA in the total transcriptome of Mycobacterium tuberculosis. PLoS Pathog 7, e1002342. [View Article][PubMed] [Google Scholar]
  2. Bashan A., Yonath A.(2008). Correlating ribosome function with high-resolution structures. Trends Microbiol 16, 326335. [View Article][PubMed] [Google Scholar]
  3. Beste D. J., Peters J., Hooper T., Avignone-Rossa C., Bushell M. E., McFadden J.(2005). Compiling a molecular inventory for Mycobacterium bovis BCG at two growth rates: evidence for growth rate-mediated regulation of ribosome biosynthesis and lipid metabolism. J Bacteriol 187, 16771684. [View Article][PubMed] [Google Scholar]
  4. Brown-Elliott B. A., Wallace R. J. Jr(2002). Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin Microbiol Rev 15, 716746. [View Article][PubMed] [Google Scholar]
  5. Burmann B. M., Luo X., Rösch P., Wahl M. C., Gottesman M. E.(2010). Fine tuning of the E. coli NusB : NusE complex affinity to BoxA RNA is required for processive antitermination. Nucleic Acids Res 38, 314326. [View Article][PubMed] [Google Scholar]
  6. Byrne R., Levin J. G., Bladen H. A., Nirenberg M. W.(1964). The in vitro formation of a DNA-ribosome complex. Proc Natl Acad Sci U S A 52, 140148. [View Article][PubMed] [Google Scholar]
  7. Coenye T., Vandamme P.(2005). Organisation of the S10, spc and alpha ribosomal protein gene clusters in prokaryotic genomes. FEMS Microbiol Lett 242, 117126. [View Article][PubMed] [Google Scholar]
  8. Cortes T., Schubert O. T., Rose G., Arnvig K. B., Comas I., Aebersold R., Young D. B.(2013). Genome-wide mapping of transcriptional start sites defines an extensive leaderless transcriptome in Mycobacterium tuberculosis. Cell Rep 5, 11211131. [View Article][PubMed] [Google Scholar]
  9. Cox R. A.(2004). Quantitative relationships for specific growth rates and macromolecular compositions of Mycobacterium tuberculosis, Streptomyces coelicolor A3(2) and Escherichia coli B/r: an integrative theoretical approach. Microbiology 150, 14131426. [View Article][PubMed] [Google Scholar]
  10. Cox M. P., Peterson D. A., Biggs P. J.(2010). SolexaQA: at-a-glance quality assessment of Illumina second-generation sequencing data. BMC Bioinformatics 11, 485. [View Article][PubMed] [Google Scholar]
  11. Gonzalez-y-Merchand J. A., Colston M. J., Cox R. A.(1996). The rRNA operons of Mycobacterium smegmatis and Mycobacterium tuberculosis: comparison of promoter elements and of neighbouring upstream genes. Microbiology 142, 667674. [View Article][PubMed] [Google Scholar]
  12. Gonzalez-y-Merchand J. A., Garcia M. J., Gonzalez-Rico S., Colston M. J., Cox R. A.(1997). Strategies used by pathogenic and nonpathogenic mycobacteria to synthesize rRNA. J Bacteriol 179, 69496958.[PubMed] [Google Scholar]
  13. Gopal B., Cox R. A., Colston M. J., Dodson G. G., Smerdon S. J., Haire L. F.(2000a). Crystallization and preliminary X-ray diffraction studies on the N-utilizing substance-B (NusB) from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr 56, 6466. [View Article][PubMed] [Google Scholar]
  14. Gopal B., Haire L. F., Cox R. A., Colston M. J., Major S., Brannigan J. A., Smerdon S. J., Dodson G.(2000b). The crystal structure of NusB from Mycobacterium tuberculosis. Nat Struct Biol 7, 475478. [View Article][PubMed] [Google Scholar]
  15. Ji Y., Colston M. J., Cox R. A.(1994a). The ribosomal RNA (rrn) operons of fast-growing mycobacteria: primary and secondary structures and their relation to rrn operons of pathogenic slow-growers. Microbiology 140, 28292840. [View Article][PubMed] [Google Scholar]
  16. Ji Y., Colston M. J., Cox R. A.(1994b). Nucleotide sequence and secondary structures of precursor 16S rRNA of slow-growing mycobacteria. Microbiology 140, 123132. [View Article][PubMed] [Google Scholar]
  17. Ji Y., Kempsell K. E., Colston M. J., Cox R. A.(1994c). Nucleotide sequences of the spacer-1, spacer-2 and trailer regions of the rrn operons and secondary structures of precursor 23S rRNAs and precursor 5S rRNAs of slow-growing mycobacteria. Microbiology 140, 17631773. [View Article][PubMed] [Google Scholar]
  18. Kempsell K. E., Ji Y., Estrada-G I. C. E., Colston M. J., Cox R. A.(1992). The nucleotide sequence of the promoter, 16S rRNA and spacer region of the ribosomal RNA operon of Mycobacterium tuberculosis and comparison with Mycobacterium leprae precursor rRNA. J Gen Microbiol 138, 17171727. [View Article][PubMed] [Google Scholar]
  19. Li H., Durbin R.(2009). Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 17541760. [View Article][PubMed] [Google Scholar]
  20. Mattheakis L., Vu L., Sor F., Nomura M.(1989). Retroregulation of the synthesis of ribosomal proteins L14 and L24 by feedback repressor S8 in Escherichia coli. Proc Natl Acad Sci U S A 86, 448452. [View Article][PubMed] [Google Scholar]
  21. McGary K., Nudler E.(2013). RNA polymerase and the ribosome: the close relationship. Curr Opin Microbiol 16, 112117. [View Article][PubMed] [Google Scholar]
  22. Miller O. L. Jr, Hamkalo B. A.(1972).Functional Units in Protein Biosynthesis ( FEBS Symposium no. 23). London: Academic Press. [Google Scholar]
  23. Miller O. L. Jr, Hamkalo B. A., Thomas C. A. Jr(1970). Visualization of bacterial genes in action. Science 169, 392395. [View Article][PubMed] [Google Scholar]
  24. Proshkin S., Rahmouni A. R., Mironov A., Nudler E.(2010). Cooperation between translating ribosomes and RNA polymerase in transcription elongation. Science 328, 504508. [View Article][PubMed] [Google Scholar]
  25. Quinlan A. R., Hall I. M.(2010). BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841842. [View Article][PubMed] [Google Scholar]
  26. Ripoll F., Pasek S., Schenowitz C., Dossat C., Barbe V., Rottman M., Macheras E., Heym B., Herrmann J. L. et al.(2009). Non mycobacterial virulence genes in the genome of the emerging pathogen Mycobacterium abscessus. PLoS ONE 4, e5660. [View Article][PubMed] [Google Scholar]
  27. Schaechter M., Maaloe O., Kjeldgaard N. O.(1958). Dependency on medium and temperature of cell size and chemical composition during balanced grown of Salmonella typhimurium. J Gen Microbiol 19, 592606. [View Article][PubMed] [Google Scholar]
  28. Stelzl U., Zengel J. M., Tovbina M., Walker M., Nierhaus K. H., Lindahl L., Patel D. J.(2003). RNA-structural mimicry in Escherichia coli ribosomal protein L4-dependent regulation of the S10 operon. J Biol Chem 278, 2823728245. [View Article][PubMed] [Google Scholar]
  29. Stent G. S.(1964). The operon: on its third anniversary. Modulation of transfer RNA species can provide a workable model of an operator-less operon. Science 144, 816820. [View Article][PubMed] [Google Scholar]
  30. Tobin D. M., Ramakrishnan L.(2008). Comparative pathogenesis of Mycobacterium marinum and Mycobacterium tuberculosis. Cell Microbiol 10, 10271039. [View Article][PubMed] [Google Scholar]
  31. Williamson J. R.(2009). The ribosome at atomic resolution. Cell 139, 10411043. [View Article][PubMed] [Google Scholar]

Data & Media loading...


Supplementary Data

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error