Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Prokaryotic transcriptomics: a new view on regulation, physiology and pathogenicity

Abstract

Transcriptome-wide studies in eukaryotes have been instrumental in the characterization of fundamental regulatory mechanisms for more than a decade. By contrast, in prokaryotes (bacteria and archaea) whole-transcriptome studies have not been performed until recently owing to the general view that microbial gene structures are simple, as well as technical difficulties in enriching for mRNAs that lack poly(A) tails. Deep RNA sequencing and tiling array studies are now revolutionizing our understanding of the complexity, plasticity and regulation of microbial transcriptomes.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Contribution of transcriptomics to annotation of functional elements.
Figure 2: Multifunctional RNA elements in Listeria monocytogenes.
Figure 3: Metatranscriptomics: a flow diagram of the steps involved in metatranscriptome sequencing and analysis.

References

  1. Strausberg, R. L. & Riggins, G. J. Navigating the human transcriptome. Proc. Natl Acad. Sci. USA 98, 11837–11838 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wang, Z., Gerstein, M. & Snyder, M. RNA-Seq: a revolutionary tool for transcriptomics. Nature Rev. Genet. 10, 57–63 (2009).

    Article  CAS  PubMed  Google Scholar 

  3. Xing, Y. & Lee, C. Alternative splicing and RNA selection pressure — evolutionary consequences for eukaryotic genomes. Nature Rev. Genet. 7, 499–509 (2006).

    Article  CAS  PubMed  Google Scholar 

  4. Misra, S. et al. Annotation of the Drosophila melanogaster euchromatic genome: a systematic review. Genome Biol. 3, research0083 (2002).

  5. Kiyosawa, H., Yamanaka, I., Osato, N., Kondo, S. & Hayashizaki, Y. Antisense transcripts with FANTOM2 clone set and their implications for gene regulation. Genome Res. 13, 1324–1334 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yelin, R. et al. Widespread occurrence of antisense transcription in the human genome. Nature Biotech. 21, 379–386 (2003).

    Article  CAS  Google Scholar 

  7. He, Y., Vogelstein, B., Velculescu, V. E., Papadopoulos, N. & Kinzler, K. W. The antisense transcriptomes of human cells. Science 322, 1855–1857 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Neidhardt, F. C. et al. Escherichia coli and Salmonella: Cellular and Molecular Biology (ed. Neidhardt, F. C.) 13–16 (ASM Press, Washington, DC, 1996).

    Google Scholar 

  9. Bryant, P. A., Venter, D., Robins-Browne, R. & Curtis, N. Chips with everything: DNA microarrays in infectious diseases. Lancet Infect. Dis. 4, 100–111 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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  Google Scholar 

  12. 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  Google Scholar 

  13. 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 

  14. Guell, M. et al. Transcriptome complexity in a genome-reduced bacteria. Science (in the press).

  15. Wurtzel, O. et al. A single-base resolution map of an archaeal transcriptome Genome Res. 2 Nov 2009 (doi:10.1101/gr.100396.109).

    Article  PubMed  Google Scholar 

  16. 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 

  17. 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 

  18. Toledo-Arana, A. et al. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459, 950–956 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Koide, T. et al. Prevalence of transcription promoters within archaeal operons and coding sequences. Mol. Syst. Biol. 5, 285 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  20. 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 

  21. 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 

  22. McHardy, A. C., Goesmann, A., Puhler, A. & Meyer, F. Development of joint application strategies for two microbial gene finders. Bioinformatics 20, 1622–1631 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Overbeek, R., Bartels, D., Vonstein, V. & Meyer, F. Annotation of bacterial and archaeal genomes: improving accuracy and consistency. Chem. Rev. 107, 3431–3447 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. Coppins, R. L., Hall, K. B. & Groisman, E. A. The intricate world of riboswitches. Curr. Opin. Microbiol. 10, 176–181 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mandal, M., Boese, B., Barrick, J. E., Winkler, W. C. & Breaker, R. R. Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell 113, 577–586 (2003).

    Article  CAS  PubMed  Google Scholar 

  27. Hammann, C. & Westhof, E. Searching genomes for ribozymes and riboswitches. Genome Biol. 8, 210 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Brenneis, M., Hering, O., Lange, C. & Soppa, J. Experimental characterization of cis-acting elements important for translation and transcription in halophilic archaea. PLoS Genet. 3, e229 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Brenneis, M. & Soppa, J. Regulation of translation in haloarchaea: 5′- and 3′-UTRs are essential and have to functionally interact in vivo. PLoS ONE 4, e4484 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mao, F., Dam, P., Chou, J., Olman, V. & Xu, Y. DOOR: a database for prokaryotic operons. Nucleic Acids Res. 37, D459–D463 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. 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 

  32. 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 

  33. Toledo-Arana, A., Repoila, F. & Cossart, P. Small noncoding RNAs controlling pathogenesis. Curr. Opin. Microbiol. 10, 182–188 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Aiba, H. Mechanism of RNA silencing by Hfq-binding small RNAs. Curr. Opin. Microbiol. 10, 134–139 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Livny, J. & Waldor, M. K. Identification of small RNAs in diverse bacterial species. Curr. Opin. Microbiol. 10, 96–101 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Zhang, A. et al. Global analysis of small RNA and mRNA targets of Hfq. Mol. Microbiol. 50, 1111–1124 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Lavorgna, G. et al. In search of antisense. Trends Biochem. Sci. 29, 88–94 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  39. Georg, J. et al. Evidence for a major role of antisense RNAs in cyanobacterial gene regulation. Mol. Syst. Biol. 5, 305 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Liu, J. M. et al. Experimental discovery of sRNAs in Vibrio cholerae by direct cloning, 5S/tRNA depletion and parallel sequencing. Nucleic Acids Res. 37, e46 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Loh, E. et al. A trans- acting riboswitch controls expression of the virulence regulator PrfA in Listeria monocytogenes. Cell 139, 770–779 (2009).

    Article  CAS  PubMed  Google Scholar 

  42. Pace, N. R. A molecular view of microbial diversity and the biosphere. Science 276, 734–740 (1997).

    Article  CAS  PubMed  Google Scholar 

  43. Tringe, S. G. & Rubin, E. M. Metagenomics: DNA sequencing of environmental samples. Nature Rev. Genet. 6, 805–814 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Tringe, S. G. et al. Comparative metagenomics of microbial communities. Science 308, 554–557 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. DeLong, E. F. et al. Community genomics among stratified microbial assemblages in the ocean's interior. Science 311, 496–503 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Rusch, D. B. et al. The Sorcerer II Global Ocean Sampling expedition: northwest Atlantic through eastern tropical Pacific. PLoS Biol. 5, e77 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  47. DeLong, E. F. The microbial ocean from genomes to biomes. Nature 459, 200–206 (2009).

    Article  CAS  PubMed  Google Scholar 

  48. Warnecke, F. et al. Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite. Nature 450, 560–565 (2007).

    Article  CAS  PubMed  Google Scholar 

  49. Poretsky, R. S. et al. Analysis of microbial gene transcripts in environmental samples. Appl. Environ. Microbiol. 71, 4121–4126 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Leininger, S. et al. Archaea predominate among ammonia-oxidizing prokaryotes in soils. Nature 442, 806–809 (2006).

    Article  CAS  PubMed  Google Scholar 

  51. Gilbert, J. A. et al. Detection of large numbers of novel sequences in the metatranscriptomes of complex marine microbial communities. PLoS ONE 3, e3042 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Urich, T. et al. Simultaneous assessment of soil microbial community structure and function through analysis of the meta-transcriptome. PLoS ONE 3, e2527 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Shi, Y., Tyson, G. W. & DeLong, E. F. Metatranscriptomics reveals unique microbial small RNAs in the ocean's water column. Nature 459, 266–269 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Kaern, M., Elston, T. C., Blake, W. J. & Collins, J. J. Stochasticity in gene expression: from theories to phenotypes. Nature Rev. Genet. 6, 451–464 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  56. Mao, C., Evans, C., Jensen, R. V. & Sobral, B. W. Identification of new genes in Sinorhizobium meliloti using the Genome Sequencer FLX system. BMC Microbiol. 8, 72 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Amara, R. R. & Vijaya, S. Specific polyadenylation and purification of total messenger RNA from Escherichia coli. Nucleic Acids Res. 25, 3465–3470 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wendisch, V. F. et al. Isolation of Escherichia coli mRNA and comparison of expression using mRNA and total RNA on DNA microarrays. Anal. Biochem. 290, 205–213 (2001).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank O. Wurtzel and A. Levy for stimulating comments. R.S. is supported, in part, by the Israel Science Foundation Focal Initiatives in Research in Science and Technology (FIRST) program (grant 1615/09), the Crown Human Genome Center, the Y. Leon Benoziyo Institute for Molecular Medicine and the M.D. Moross Institute for Cancer Research at the Weizmann Institute of Science, as well as the Alon Fellowship. P.C. is a Howard Hughes International Scholar. She has received financial support for her work on RNA from the Agence Nationale de la Recherche, the European Union (BacRNA 2005-018618) and recently from the European Research Council.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rotem Sorek.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Rotem Sorek's homepage

Pascale Cossart's homepage

Glossary

Expressed sequence tag

A fragment of cDNA that is generated using random shotgun sequencing of the transcriptome.

Genomic tiling array

A DNA microarray that uses a set of overlapping oligonucleotide probes that cover the whole genome or a proportion of the genome at high resolution.

Polycistronic mRNA

An mRNA (also known as a polycistron) that encodes several polypeptides. Polycistronic transcripts are common in bacteria.

Quorum sensing

A mechanism used by many bacteria to detect a critical bacterial cell density. Some genes are only expressed at high cell density. Cell densities are proportional to the concentration of small molecules or peptides (autoinducers) that are secreted by the bacteria in the medium. These molecules coordinate the expression of specific genes — for example, virulence genes in pathogenic bacteria.

Riboswitch

An RNA element that is located at the 5′ end of an mRNA and that can adopt alternative structures. When a riboswitch binds a metabolite, metal or even a tRNA, the transcription of the downstream gene or, in some cases, the translation of the gene is inhibited.

RNA–seq

An approach for whole-transcriptome profiling in which a population of RNA is converted to cDNA and subjected to high-throughput sequencing. Sequences are mapped to the genome to generate a high-resolution transcriptome map.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sorek, R., Cossart, P. Prokaryotic transcriptomics: a new view on regulation, physiology and pathogenicity. Nat Rev Genet 11, 9–16 (2010). https://doi.org/10.1038/nrg2695

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg2695

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing