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Bacterial transcriptomics: what is beyond the RNA horiz-ome?

Nature Reviews Microbiology volume 9, pages 658–669 (2011)Cite this article

Subjects

Key Points

  • Recent technical advances in the transcriptomics field (such as high-resolution tiling arrays and ultrasequencing) have revealed a high level of complexity in bacteria that had not been foreseen.

  • High-throughput transcript analysis has shown an unexpected abundance of small RNAs, which account for up to 27% of the bacterial genome. Some of them have regulatory roles, although most remain to be characterized.

  • The classical operon concept seems not to hold for most of the bacterial transcriptomes that have been analysed, with internal promoter and termination signals resulting in a plethora of different transcripts.

  • Like eukaryotic promoters, many bacterial promoters can be regulated by more than one transcription factor.

  • Recent studies have shown that like eukaryotic chromatin, bacterial chromatin is organized in a precise manner, and this precise organization can influence gene expression.

  • In addition to using methylation status to differentiate foreign DNA from their own DNA, bacteria are able to make epigenetic modifications to their DNA similar to those seen in eukaryotes. This status can be inherited and can change transcription of particular genes.

  • There is ample evidence that mRNA can be processed, polyadenylated and subjected to other post-transcriptional modifications.

  • Long untranslated regions have been revealed by 'omics' studies; some have regulatory regions, whereas other leaderless mRNAs seem to be translated by a different mechanism.

Abstract

Over the past 3 years, bacterial transcriptomics has undergone a massive revolution. Increased sequencing capacity and novel tools have made it possible to explore the bacterial transcriptome to an unprecedented depth, which has revealed that the transcriptome is more complex and dynamic than expected. Alternative transcripts within operons challenge the classic operon definition, and many small RNAs involved in the regulation of transcription, translation and pathogenesis have been discovered. Furthermore, mRNAs may localize to specific areas in the cell, and the spatial organization and dynamics of the chromosome have been shown to be important for transcription. Epigenetic modifications of DNA also affect transcription, and RNA processing affects translation. Therefore, transcription in bacteria resembles that in eukaryotes in terms of complexity more closely than was previously thought. Here we will discuss the contribution of 'omics' approaches to these discoveries as well as the possible impact that they are expected to have in the future.

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Figure 1: Methodological transcriptomics tool kit.
Figure 2: Recent discoveries in bacterial transcriptomics.
Figure 3: Perspectives in transcriptomics.

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References

  1. Jacob, F. & Monod, J. [Genes of structure and genes of regulation in the biosynthesis of proteins]. C. R. Hebd Seances Acad. Sci. 249, 1282–1284 (1959).

    CAS  PubMed  Google Scholar 

  2. Jacob, F. & Monod, J. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3, 318–356 (1961).

    Article  CAS  PubMed  Google Scholar 

  3. Wosten, M. M. Eubacterial sigma-factors. FEMS Microbiol. Rev. 22, 127–150 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Paget, M. S. & Helmann, J. D. The sigma70 family of sigma factors. Genome Biol. 4, 203 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Perez-Rueda, E. & Collado-Vides, J. The repertoire of DNA-binding transcriptional regulators in Escherichia coli K-12. Nucleic Acids Res. 28, 1838–1847 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Santangelo, T. J. & Artsimovitch, I. Termination and antitermination: RNA polymerase runs a stop sign Nature Rev. Microbiol. 9, 319–329 (2011).

    Article  CAS  Google Scholar 

  7. Shine, J. & Dalgarno, L. Determinant of cistron specificity in bacterial ribosomes. Nature 254, 34–38 (1975).

    Article  CAS  PubMed  Google Scholar 

  8. Sigmund, C. D. & Morgan, E. A. Nus A protein affects transcriptional pausing and termination in vitro by binding to different sites on the transcription complex. Biochemistry 27, 5622–5627 (1988).

    Article  CAS  PubMed  Google Scholar 

  9. Ma, J. C., Newman, A. J. & Hayward, R. S. Internal promoters of the rpoBC operon of Escherichia coli. Mol. Gen. Genet. 184, 548–550 (1981).

    Article  CAS  PubMed  Google Scholar 

  10. Andre, G. et al. S-box and T-box riboswitches and antisense RNA control a sulfur metabolic operon of Clostridium acetobutylicum. Nucleic Acids Res. 36, 5955–5969 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Winkler, W., Nahvi, A. & Breaker, R. R. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419, 952–956 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Boni, I. V., Artamonova, V. S., Tzareva, N. V. & Dreyfus, M. Non-canonical mechanism for translational control in bacteria: synthesis of ribosomal protein S1. EMBO J. 20, 4222–4232 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Laursen, B. S., Sorensen, H. P., Mortensen, K. K. & Sperling-Petersen, H. U. Initiation of protein synthesis in bacteria. Microbiol. Mol. Biol. Rev. 69, 101–123 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sorek, R. & Cossart, P. Prokaryotic transcriptomics: a new view on regulation, physiology and pathogenicity. Nature Rev. Genet. 11, 9–16 (2010). A complete compilation of advances in bacterial transcriptomics.

    Article  CAS  PubMed  Google Scholar 

  15. Serganov, A. & Patel, D. J. Ribozymes, riboswitches and beyond: regulation of gene expression without proteins. Nature Rev. Genet. 8, 776–790 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Makita, Y., Nakao, M., Ogasawara, N. & Nakai, K. DBTBS: database of transcriptional regulation in Bacillus subtilis and its contribution to comparative genomics. Nucleic Acids Res. 32, D75–D77 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. de Hoon, M. J., Makita, Y., Nakai, K. & Miyano, S. Prediction of transcriptional terminators in Bacillus subtilis and related species. PLoS Comput. Biol. 1, e25 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Vogel, J. et al. RNomics in Escherichia coli detects new sRNA species and indicates parallel transcriptional output in bacteria. Nucleic Acids Res. 31, 6435–6443 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Schena, M., Shalon, D., Davis, R. W. & Brown, P. O. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467–470 (1995).

    Article  CAS  PubMed  Google Scholar 

  20. Selinger, D. W. et al. RNA expression analysis using a 30 base pair resolution Escherichia coli genome array. Nature Biotech. 18, 1262–1268 (2000).

    Article  CAS  Google Scholar 

  21. Guell, M. et al. Transcriptome complexity in a genome-reduced bacterium. Science 326, 1268–1271 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. McGrath, P. T. et al. High-throughput identification of transcription start sites, conserved promoter motifs and predicted regulons. Nature Biotech. 25, 584–592 (2007).

    Article  CAS  Google Scholar 

  23. Rasmussen, S., Nielsen, H. B. & Jarmer, H. The transcriptionally active regions in the genome of Bacillus subtilis. Mol. Microbiol. 73, 1043–1057 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Perocchi, F., Xu, Z., Clauder-Munster, S. & Steinmetz, L. M. Antisense artifacts in transcriptome microarray experiments are resolved by actinomycin D. Nucleic Acids Res. 35, e128 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Johnson, J. M., Edwards, S., Shoemaker, D. & Schadt, E. E. Dark matter in the genome: evidence of widespread transcription detected by microarray tiling experiments. Trends Genet. 21, 93–102 (2005).

    Article  CAS  PubMed  Google Scholar 

  26. Royce, T. E. et al. Issues in the analysis of oligonucleotide tiling microarrays for transcript mapping. Trends Genet. 21, 466–475 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wilhelm, B. T. et al. Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution. Nature 453, 1239–1243 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Wang, Z., Gerstein, M. & Snyder, M. RNA-Seq: a revolutionary tool for transcriptomics. Nature Rev. Genet. 10, 57–63 (2009). A good introduction to RNA-seq.

    Article  CAS  PubMed  Google Scholar 

  29. Vivancos, A. P., Guell, M., Dohm, J. C., Serrano, L. & Himmelbauer, H. Strand specific deep sequencing of the transcriptome. Genome Res. 19, 255–265 (2009).

    Google Scholar 

  30. Valen, E. et al. Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE. Genome Res. 19, 255–265 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wurtzel, O. et al. A single-base resolution map of an archaeal transcriptome. Genome Res. 20, 133–141 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sharma, A. et al. Helicobacter pylori single-stranded DNA binding protein — functional characterization and modulation of H. pylori DnaB helicase activity. FEBS J. 276, 519–531 (2009).

    Article  CAS  PubMed  Google Scholar 

  33. Frias-Lopez, J. et al. Microbial community gene expression in ocean surface waters. Proc. Natl Acad. Sci. USA 105, 3805–3810 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gloor, G. B. et al. Microbiome profiling by illumina sequencing of combinatorial sequence-tagged PCR products. PLoS ONE 5, e15406 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Murakawa, G. J., Kwan, C., Yamashita, J. & Nierlich, D. P. Transcription and decay of the lac messenger: role of an intergenic terminator. J. Bacteriol. 173, 28–36 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Laing, E., Mersinias, V., Smith, C. P. & Hubbard, S. J. Analysis of gene expression in operons of Streptomyces coelicolor. Genome Biol. 7, R46 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Petersohn, A., Antelmann, H., Gerth, U. & Hecker, M. Identification and transcriptional analysis of new members of the sigmaB regulon in Bacillus subtilis. Microbiology 145, 869–880 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Perkins, J. B., Bower, S., Howitt, C. L., Yocum, R. R. & Pero, J. Identification and characterization of transcripts from the biotin biosynthetic operon of Bacillus subtilis. J. Bacteriol. 178, 6361–6365 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. McDaniel, B. A., Grundy, F. J., Artsimovitch, I. & Henkin, T. M. Transcription termination control of the S box system: direct measurement of S-adenosylmethionine by the leader RNA. Proc. Natl Acad. Sci. USA 100, 3083–3088 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sharma, C. M. et al. The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464, 250–255 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Lee, H. J., Jeon, H. J., Ji, S. C., Yun, S. H. & Lim, H. M. Establishment of an mRNA gradient depends on the promoter: an investigation of polarity in gene expression. J. Mol. Biol. 378, 318–327 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Haugen, S. P., Ross, W. & Gourse, R. L. Advances in bacterial promoter recognition and its control by factors that do not bind DNA. Nature Rev. Microbiol. 6, 507–519 (2008).

    Article  CAS  Google Scholar 

  43. Kuhner, S. et al. Proteome organization in a genome-reduced bacterium. Science 326, 1235–1240 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Proshkin, S., Rahmouni, A. R., Mironov, A. & Nudler, E. Cooperation between translating ribosomes and RNA polymerase in transcription elongation. Science 328, 504–508 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Clarke, J. et al. Continuous base identification for single-molecule nanopore DNA sequencing. Nature Nanotechnol. 4, 265–270 (2009).

    Article  CAS  Google Scholar 

  46. Eid, J. et al. Real-time DNA sequencing from single polymerase molecules. Science 323, 133–138 (2009).

    Article  CAS  PubMed  Google Scholar 

  47. Churchman, L. S. & Weissman, J. S. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 469, 368–373 (2011).

    Article  CAS  PubMed  Google Scholar 

  48. Barnard, A., Wolfe, A. & Busby, S. Regulation at complex bacterial promoters: how bacteria use different promoter organizations to produce different regulatory outcomes. Curr. Opin. Microbiol. 7, 102–108 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Kovacikova, G. & Skorupski, K. Overlapping binding sites for the virulence gene regulators AphA, AphB and cAMP-CRP at the Vibrio cholera tcpPH promoter. Mol. Microbiol. 41, 393–407 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Ptashne, M. Regulation of transcription: from lambda to eukaryotes. Trends Biochem. Sci. 30, 275–279 (2005).

    Article  CAS  PubMed  Google Scholar 

  51. Xu, Z. et al. Bidirectional promoters generate pervasive transcription in yeast. Nature 457, 1033–1037 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Trinklein, N. D. et al. An abundance of bidirectional promoters in the human genome. Genome Res. 14, 62–66 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Escolar, L., Pérez-Martin, J. & de Lorenzo, V. Coordinated repression in vitro of the divergent fepA-fes promoters of Escherichia coli by the iron uptake regulation (Fur) protein. J. Bacteriol. 180, 2579–2582 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Nieuwkoop, A. J., Baldauf, S. A., Hudspeth, M. E. & Bender, R. A. Bidirectional promoter in the hut(P) region of the histidine utilization (hut) operons from Klebsiella aerogenes. J. Bacteriol. 170, 2240–2246 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Li, Y. Y. et al. Systematic analysis of head-to-head gene organization: evolutionary conservation and potential biological relevance. PLoS Comput. Biol. 2, e74 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Munson, G. P. & Scott, J. R. Rns, a virulence regulator within the AraC family, requires binding sites upstream and downstream of its own promoter to function as an activator. Mol. Microbiol. 36, 1391–1402 (2000).

    Article  CAS  PubMed  Google Scholar 

  57. Isalan, M. et al. Evolvability and hierarchy in rewired bacterial gene networks. Nature 452, 840–845 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Matthews, K. S. DNA looping. Microbiol. Rev. 56, 123–136 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Shin, M. et al. DNA looping-mediated repression by histone-like protein H-NS: specific requirement of Esigma70 as a cofactor for looping. Genes Dev. 19, 2388–2398 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Toledo-Arana, A. et al. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459, 950–956 (2009). Complete article describing a major pathogen transcriptome.

    Article  CAS  PubMed  Google Scholar 

  61. Hershberg, R., Altuvia, S. & Margalit, H. A survey of small RNA-encoding genes in Escherichia coli. Nucleic Acids Res. 31, 1813–1820 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Brantl, S. Regulatory mechanisms employed by cis-encoded antisense RNAs. Curr. Opin. Microbiol. 10, 102–109 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Delihas, N. Regulation of gene expression by trans-encoded antisense RNAs. Mol. Microbiol. 15, 411–414 (1995).

    Article  CAS  PubMed  Google Scholar 

  64. Storz, G., Opdyke, J. A. & Zhang, A. Controlling mRNA stability and translation with small, noncoding RNAs. Curr. Opin. Microbiol. 7, 140–144 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Gottesman, S. & Storz, G. Bacterial small RNA regulators: versatile roles and rapidly evolving variations. Cold Spring Harb. Perspect. Biol. 27 Oct 2010 (doi: 10.1101/cshperspect.a003798).

    Google Scholar 

  66. Hayes, C. S. & Keiler, K. C. Beyond ribosome rescue: tmRNA and co-translational processes. FEBS Lett. 584, 413–419 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wassarman, K. M. 6S RNA: a small RNA regulator of transcription. Curr. Opin. Microbiol. 10, 164–168 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Waters, L. S. & Storz, G. Regulatory RNAs in bacteria. Cell 136, 615–628 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Cook, D. N., Ma, D., Pon, N. G. & Hearst, J. E. Dynamics of DNA supercoiling by transcription in Escherichia coli. Proc. Natl Acad. Sci. USA 89, 10603–10607 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Blot, N., Mavathur, R., Geertz, M., Travers, A. & Muskhelishvili, G. Homeostatic regulation of supercoiling sensitivity coordinates transcription of the bacterial genome. EMBO Rep. 7, 710–715 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gottesman, S. Micros for microbes: non-coding regulatory RNAs in bacteria. Trends Genet. 21, 399–404 (2005). A good review of the roles of sRNAs in bacteria.

    Article  CAS  PubMed  Google Scholar 

  72. Bejerano-Sagie, M. & Xavier, K. B. The role of small RNAs in quorum sensing. Curr. Opin. Microbiol. 10, 189–198 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Masse, E., Salvail, H., Desnoyers, G. & Arguin, M. Small RNAs controlling iron metabolism. Curr. Opin. Microbiol. 10, 140–145 (2007).

    Article  CAS  PubMed  Google Scholar 

  74. Papenfort, K., Bouvier, M., Mika, F., Sharma, C. M. & Vogel, J. Evidence for an autonomous 5′ target recognition domain in an Hfq-associated small RNA. Proc. Natl Acad. Sci. USA 107, 20435–20440 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Balbontin, R., Fiorini, F., Figueroa-Bossi, N., Casadesus, J. & Bossi, L. Recognition of heptameric seed sequence underlies multi-target regulation by RybB small RNA in Salmonella enterica. Mol. Microbiol. 78, 380–394 (2010).

    Article  CAS  PubMed  Google Scholar 

  76. Mitarai, N., Andersson, A. M., Krishna, S., Semsey, S. & Sneppen, K. Efficient degradation and expression prioritization with small RNAs. Phys. Biol. 4, 164–171 (2007).

    Article  CAS  PubMed  Google Scholar 

  77. Qiu, Y. et al. Structural and operational complexity of the Geobacter sulfurreducens genome. Genome Res. 20, 1304–1311 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Dornenburg, J. E., Devita, A. M., Palumbo, M. J. & Wade, J. T. Widespread antisense transcription in Escherichia coli. MBio 1, e00024-10 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Ge, X., Wu, Q., Jung, Y. C., Chen, J. & Wang, S. M. A large quantity of novel human antisense transcripts detected by LongSAGE. Bioinformatics 22, 2475–2479 (2006).

    Article  CAS  PubMed  Google Scholar 

  80. Henz, S. R. et al. Distinct expression patterns of natural antisense transcripts in Arabidopsis. Plant Physiol. 144, 1247–1255 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yoder-Himes, D. R. et al. Mapping the Burkholderia cenocepacia niche response via high-throughput sequencing. Proc. Natl Acad. Sci. USA 106, 3976–3981 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Perkins, T. T. et al. A strand-specific RNA–Seq analysis of the transcriptome of the typhoid bacillus Salmonella Typhi. PLoS Genet. 5, e1000569 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Sittka, A. et al. Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator, Hfq. PLoS Genet. 4, e1000163 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Passalacqua, K. D. et al. Structure and complexity of a bacterial transcriptome. J. Bacteriol. 191, 3203–3211 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Denoeud, F. et al. Prominent use of distal 5′ transcription start sites and discovery of a large number of additional exons in ENCODE regions. Genome Res. 17, 746–759 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Schluter, J. P. et al. A genome-wide survey of sRNAs in the symbiotic nitrogen fixing alpha-proteobacterium Sinorhizobium meliloti. BMC Genomics 11, 245 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Wassarman, K. M. & Saecker, R. M. Synthesis-mediated release of a small RNA inhibitor of RNA polymerase. Science 314, 1601–1603 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Novick, R. P. & Geisinger, E. Quorum sensing in staphylococci. Annu. Rev. Genet. 42, 541–564 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Vanderpool, C. K. & Gottesman, S. Involvement of a novel transcriptional activator and small RNA in post-transcriptional regulation of the glucose phosphoenolpyruvate phosphotransferase system. Mol. Microbiol. 54, 1076–1089 (2004).

    Article  CAS  PubMed  Google Scholar 

  90. Wadler, C. S. & Vanderpool, C. K. A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide. Proc. Natl Acad. Sci. USA 104, 20454–20459 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Maki, K., Morita, T., Otaka, H. & Aiba, H. A minimal base-pairing region of a bacterial small RNA SgrS required for translational repression of ptsG mRNA. Mol. Microbiol. 76, 782–792 (2010).

    Article  CAS  PubMed  Google Scholar 

  92. Bouamrani, A. et al. Mesoporous silica chips for selective enrichment and stabilization of low molecular weight proteome. Proteomics 10, 496–505 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Chang, S. J., Hsieh, S. Y., Yuan, H. S. & Chak, K. F. Characterization of the specific cleavage of ceiE7-mRNA of the bactericidal ColE7 operon. Biochem. Biophys. Res. Commun. 299, 613–620 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. Anderson, K. L. & Dunman, P. M. Messenger RNA turnover processes in Escherichia coli, Bacillus subtilis, and emerging studies in Staphylococcus aureus. Int. J. Microbiol. 2009, 525491 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Deana, A., Celesnik, H. & Belasco, J. G. The bacterial enzyme RppH triggers messenger RNA degradation by 5′ pyrophosphate removal. Nature 451, 355–358 (2008).

    Article  CAS  PubMed  Google Scholar 

  96. Richards, J., Sundermeier, T., Svetlanov, A. & Karzai, A. W. Quality control of bacterial mRNA decoding and decay. Biochim. Biophys. Acta 1779, 574–582 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kime, L., Jourdan, S. S., Stead, J. A., Hidalgo-Sastre, A. & McDowall, K. J. Rapid cleavage of RNA by RNase E in the absence of 5′ monophosphate stimulation. Mol. Microbiol. 76, 590–604 (2010).

    Article  CAS  PubMed  Google Scholar 

  98. Mohanty, B. K. & Kushner, S. R. Bacterial/archaeal/organellar polyadenylation. WIREs RNA 2, 256–276 (2010).

    Article  CAS  Google Scholar 

  99. Steege, D. A. Emerging features of mRNA decay in bacteria. RNA 6, 1079–1090 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Gopalakrishna, Y., Langley, D. & Sarkar, N. Detection of high levels of polyadenylate-containing RNA in bacteria by the use of a single-step RNA isolation procedure. Nucleic Acids Res. 9, 3545–3554 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Mohanty, B. K. & Kushner, S. R. The majority of Escherichia coli mRNAs undergo post-transcriptional modification in exponentially growing cells. Nucleic Acids Res. 34, 5695–5704 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Jasiecki, J. & Wegrzyn, G. Growth-rate dependent RNA polyadenylation in Escherichia coli. EMBO Rep. 4, 172–177 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Bernstein, J. A., Khodursky, A. B., Lin, P. H., Lin-Chao, S. & Cohen, S. N. Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays. Proc. Natl Acad. Sci. USA 99, 9697–9702 (2002). The first global analysis of RNA decay in bacteria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Li, Z., Reimers, S., Pandit, S. & Deutscher, M. P. RNA quality control: degradation of defective transfer RNA. EMBO J. 21, 1132–1138 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Schmitz-Linneweber, C. et al. A pentatricopeptide repeat protein facilitates the trans-splicing of the maize chloroplast rps12 pre-mRNA. Plant Cell 18, 2650–2663 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Seiwert, S. D. & Stuart, K. RNA editing: transfer of genetic information from gRNA to precursor mRNA in vitro. Science 266, 114–117 (1994).

    Article  CAS  PubMed  Google Scholar 

  107. Belfort, M. Self-splicing introns in prokaryotes: migrant fossils? Cell 64, 9–11 (1991).

    Article  CAS  PubMed  Google Scholar 

  108. Chu, F. K., Maley, G. F., Maley, F. & Belfort, M. Intervening sequence in the thymidylate synthase gene of bacteriophage T4. Proc. Natl Acad. Sci. USA 81, 3049–3053 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Toro, N. Bacteria and Archaea Group II introns: additional mobile genetic elements in the environment. Environ. Microbiol. 5, 143–151 (2003).

    Article  CAS  PubMed  Google Scholar 

  110. Krishnan, K. M., Van Etten, W. J. & Janssen, G. R. Proximity of the start codon to a leaderless mRNA's 5′ terminus is a strong positive determinant of ribosome binding and expression in Escherichia coli. J. Bacteriol. 192, 6482–6485.

  111. Brock, J. E., Pourshahian, S., Giliberti, J., Limbach, P. A. & Janssen, G. R. Ribosomes bind leaderless mRNA in Escherichia coli through recognition of their 5′-terminal AUG. RNA 14, 2159–2169 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. O'Donnell, S. M. & Janssen, G. R. Leaderless mRNAs bind 70S ribosomes more strongly than 30S ribosomal subunits in Escherichia coli. J. Bacteriol. 184, 6730–6733 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Moll, I., Hirokawa, G., Kiel, M. C., Kaji, A. & Blasi, U. Translation initiation with 70S ribosomes: an alternative pathway for leaderless mRNAs. Nucleic Acids Res. 32, 3354–3363 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Grill, S., Gualerzi, C. O., Londei, P. & Blasi, U. Selective stimulation of translation of leaderless mRNA by initiation factor 2: evolutionary implications for translation. EMBO J. 19, 4101–4110 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Yanofsky, C. Attenuation in the control of expression of bacterial operons. Nature 289, 751–758 (1981).

    Article  CAS  PubMed  Google Scholar 

  116. Fuchs, R. T., Grundy, F. J. & Henkin, T. M. The SMK box is a new SAM-binding RNA for translational regulation of SAM synthetase. Nature Struct. Mol. Biol. 13, 226–233 (2006).

    Article  CAS  Google Scholar 

  117. Fuchs, R. T., Grundy, F. J. & Henkin, T. M. S-adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the SMK box translational riboswitch RNA. Proc. Natl Acad. Sci. USA 104, 4876–4880 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Smith, A. M., Fuchs, R. T., Grundy, F. J. & Henkin, T. M. The SAM-responsive SMK box is a reversible riboswitch. Mol. Microbiol. 78, 1393–1402 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Kertesz, M. et al. Genome-wide measurement of RNA secondary structure in yeast. Nature 467, 103–107 (2010).

    Article  CAS  PubMed  Google Scholar 

  120. Underwood, J. G. et al. FragSeq: transcriptome-wide RNA structure probing using high-throughput sequencing. Nature Methods 7, 995–1001 (2010). References 119 and 120 describe promising methods for determining RNA structure in bacteria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Postow, L., Hardy, C. D., Arsuaga, J. & Cozzarelli, N. R. Topological domain structure of the Escherichia coli chromosome. Genes Dev. 18, 1766–1779 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Gitai, Z., Thanbichler, M. & Shapiro, L. The choreographed dynamics of bacterial chromosomes. Trends Microbiol. 13, 221–228 (2005).

    Article  CAS  PubMed  Google Scholar 

  123. Dillon, S. C. & Dorman, C. J. Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nature Rev. Microbiol. 8, 185–195 (2010).

    Article  CAS  Google Scholar 

  124. Peter, B. J. et al. Genomic transcriptional response to loss of chromosomal supercoiling in Escherichia coli. Genome Biol. 5, R87 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Vora, T., Hottes, A. K. & Tavazoie, S. Protein occupancy landscape of a bacterial genome. Mol. Cell 35, 247–253 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. French, S. L. & Miller, O. L. Jr. Transcription mapping of the Escherichia coli chromosome by electron microscopy. J. Bacteriol. 171, 4207–4216 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Binenbaum, Z., Parola, A. H., Zaritsky, A. & Fishov, I. Transcription- and translation-dependent changes in membrane dynamics in bacteria: testing the transertion model for domain formation. Mol. Microbiol. 32, 1173–1182 (1999).

    Article  CAS  PubMed  Google Scholar 

  128. Deng, S., Stein, R. A. & Higgins, N. P. Organization of supercoil domains and their reorganization by transcription. Mol. Microbiol. 57, 1511–1521 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Dekker, J., Rippe, K., Dekker, M. & Kleckner, N. Capturing chromosome conformation. Science 295, 1306–1311 (2002).

    Article  CAS  PubMed  Google Scholar 

  130. Dostie, J. et al. Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res. 16, 1299–1309 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. van Berkum, N. L. et al. Hi-C: a method to study the three-dimensional architecture of genomes. http://www.jove.com/details.php?id=1869doi:10.3791/1869. J. Vis. Exp. 39 (2010).

  132. Vassetzky, Y. et al. Chromosome conformation capture (from 3C to 5C) and its ChIP-based modification. Methods Mol. Biol. 567, 171–188 (2009).

    Article  CAS  PubMed  Google Scholar 

  133. Tolhuis, B., Palstra, R. J., Splinter, E., Grosveld, F. & de Laat, W. Looping and interaction between hypersensitive sites in the active β-globin locus. Mol. Cell 10, 1453–1465 (2002).

    Article  CAS  PubMed  Google Scholar 

  134. Dhar, S. S. & Wong-Riley, M. T. Chromosome conformation capture of transcriptional interactions between cytochrome c oxidase genes and genes of glutamatergic synaptic transmission in neurons. J. Neurochem. 115, 676–683 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Duan, Z. et al. A three-dimensional model of the yeast genome. Nature 465, 363–367 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Casadesus, J. & Low, D. Epigenetic gene regulation in the bacterial world. Microbiol. Mol. Biol. Rev. 70, 830–856 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Sohanpal, B. K., El-Labany, S., Lahooti, M., Plumbridge, J. A. & Blomfield, I. C. Integrated regulatory responses of fimB to N-acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12. Proc. Natl Acad. Sci. USA 101, 16322–16327 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Blyn, L. B., Braaten, B. A. & Low, D. A. Regulation of pap pilin phase variation by a mechanism involving differential dam methylation states. EMBO J. 9, 4045–4054 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Turner, K. H., Vallet-Gely, I. & Dove, S. L. Epigenetic control of virulence gene expression in Pseudomonas aeruginosa by a LysR-type transcription regulator. PLoS Genet. 5, e1000779 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Flusberg, B. A. et al. Direct detection of DNA methylation during single-molecule, real-time sequencing. Nature Methods 7, 461–465 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Shapiro, L. & Losick, R. Protein localization and cell fate in bacteria. Science 276, 712–718 (1997).

    Article  CAS  PubMed  Google Scholar 

  142. Golding, I. & Cox, E. C. RNA dynamics in live Escherichia coli cells. Proc. Natl Acad. Sci. USA 101, 11310–11315 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Llopis, P. M. et al. Spatial organization of the flow of genetic information in bacteria. Nature 466, 77–81 (2010).

    Article  CAS  PubMed Central  Google Scholar 

  144. Schoenfelder, S. et al. Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nature Genet. 42, 53–61 (2010).

    Article  CAS  PubMed  Google Scholar 

  145. Nevo-Dinur, K., Nussbaum-Shochat, A., Ben-Yehuda, S. & Amster-Choder, O. Translation-independent localization of mRNA in E. coli. Science 331, 1081–1084 (2011).

    Article  CAS  PubMed  Google Scholar 

  146. Evguenieva-Hackenberg, E., Roppelt, V., Lassek, C. & Klug, G. Subcellular localization of RNA degrading proteins and protein complexes in prokaryotes. RNA Biol. 8, 49–54 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Femino, A. M., Fay, F. S., Fogarty, K. & Singer, R. H. Visualization of single RNA transcripts in situ. Science 280, 585–590 (1998).

    Article  CAS  PubMed  Google Scholar 

  148. Santangelo, P. J. et al. Single molecule-sensitive probes for imaging RNA in live cells. Nature Methods 6, 347–349 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Taniguchi, Y. et al. Quantifying E. coli proteome and transcriptome with single molecule sensitivity in single cells. Science 329, 533–538 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Elf, J., Li, G. W. & Xie, X. S. Probing transcription factor dynamics at the single molecule level in a living cell. Science 316, 1191–1194 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Suel, G. M., Garcia-Ojalvo, J., Liberman, L. M. & Elowitz, M. B. An excitable gene regulatory circuit induces transient cellular differentiation. Nature 440, 545–550 (2006).

    Article  CAS  PubMed  Google Scholar 

  152. Tang, F. et al. mRNA-Seq whole-transcriptome analysis of a single cell. Nature Methods 6, 377–382 (2009).

    Article  CAS  PubMed  Google Scholar 

  153. Hardy, C. D. & Cozzarelli, N. R. A genetic selection for supercoiling mutants of Escherichia coli reveals proteins implicated in chromosome structure. Mol. Microbiol. 57, 1636–1652 (2005).

    Article  CAS  PubMed  Google Scholar 

  154. Flicek, P. & Birney, E. Sense from sequence reads: methods for alignment and assembly. Nature Methods 6, S6–S12 (2009).

    Article  CAS  PubMed  Google Scholar 

  155. Li, R., Li, Y., Kristiansen, K. & Wang, J. SOAP: short oligonucleotide alignment program. Bioinformatics 24, 713–714 (2008).

    Article  CAS  PubMed  Google Scholar 

  156. Li, H., Ruan, J. & Durbin, R. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res. 18, 1851–1858 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Li, R. et al. SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25, 1966–1967 (2009).

    Article  CAS  PubMed  Google Scholar 

  160. Kang, Y. et al. Transcript amplification from single bacterium for transcriptome analysis, Genome Res. 32, 925–935 (2011).

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank M. Isalan and B. Lehner for critical reading of the manuscript. This work was supported by the Consolider programme of the Spanish Ministry of Research, the Fundación Marcelino Botín and the European Research Council.

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  1. Marc Güell

    Present address: Present address: Harvard Medical School, 77 Louis Pasteur Avenue, Boston, Massachusetts 02115, USA.,

  2. Marc Güell and Eva Yus: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre for Genomic Regulation, Universitat Pompeu Fabra, Av. Dr. Aiguader 88, Barcelona, 08003, Spain

    Marc Güell, Maria Lluch-Senar & Luis Serrano

  2. ICREA (Institució Catalana de Recerca i Estudis Avançats), Passeig Lluís Companys, 23, Barcelona, 08010, Spain

    Eva Yus & Luis Serrano

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Bioconductor

Glossary

Transcriptome

The complete set of RNA molecules produced in a cell.

DNA microarrays

Technology used to carry out measurements of a large number of transcript levels simultaneously. Microarrays consist of a series of microscopic spots of DNA oligonucleotides targeting specific sequences. These probes hybridize to the target species (usually cDNA). Probe–target hybridization is quantified to determine the abundance of nucleic acid sequences in the sample.

Tiling arrays

A subtype of DNA microarray chips. Tiling arrays differ according to the nature of the probes. Probe sequences are tiled and cover the entire genome. They are used for whole-transcriptome profiling.

Deep sequencing

New sequencing te chnologies that make use of massive parallelization of the sequencing process. Data provided by these new sequencers consist of a large number of reads (millions) in each run but with a short read length (of a few hundred bases).

Cistrons

Segments of DNA that have the information to produce a polypeptide chain.

Stationary phase

A stage of bacterial growth in which the growth rate slows as a result of nutrient depletion and accumulation of toxic products.

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Güell, M., Yus, E., Lluch-Senar, M. et al. Bacterial transcriptomics: what is beyond the RNA horiz-ome?. Nat Rev Microbiol 9, 658–669 (2011). https://doi.org/10.1038/nrmicro2620

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