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.

Pervasive transcription: illuminating the dark matter of bacterial transcriptomes

Nature Reviews Microbiology volume 12, pages 647–653 (2014)Cite this article

Subjects

Abstract

The conventional view of transcription posits that mRNAs are generated from the coding DNA strand and are delineated by gene boundaries; however, recent reports have mapped transcription start sites to unexpected locations in bacterial genomes, including the non-coding strand. The resultant RNAs were previously dismissed as artefacts, but models that describe such events as 'pervasive transcription' are now gaining support. In this Opinion article, we discuss our current understanding of pervasive transcription, its genetic origin and its regulation. On the basis of existing observations, we propose that RNAs that result from pervasive transcription are more than 'transcriptional noise' and have important functions in gene regulation and genome evolution.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Sources of pervasive transcription in bacterial genomes.
Figure 2: Mechanisms for the suppression of pervasive transcription in bacteria.
Figure 3: Mechanisms by which pervasive antisense transcription modulates gene expression.

References

  1. Pearson, H. What is a gene? Nature 441, 398–401 (2006).

    Article  CAS  Google Scholar 

  2. Kapranov, P. et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316, 1484–1488 (2007).

    Article  CAS  Google Scholar 

  3. Okazaki, Y. et al. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420, 563–573 (2002).

    Article  Google Scholar 

  4. Velculescu, V. E. et al. Characterization of the yeast transcriptome. Cell 88, 243–251 (1997).

    Article  CAS  Google Scholar 

  5. 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 

  6. Slonczewski, J. L. Concerns about recently identified widespread antisense transcription in Escherichia coli. mBio 1, e00106–10 (2010).

    Article  Google Scholar 

  7. Robertson, M. The evolution of gene regulation, the RNA universe, and the vexed questions of artefact and noise. BMC Biol. 8, 97 (2010).

    Article  Google Scholar 

  8. Robinson, R. Dark matter transcripts: sound and fury, signifying nothing? PLoS Biol. 8, e1000370 (2010).

    Article  Google Scholar 

  9. van Bakel, H., Nislow, C., Blencowe, B. J. & Hughes, T. R. Most 'dark matter' transcripts are associated with known genes. PLoS Biol. 8, e1000371 (2010).

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Mitschke, J. et al. An experimentally anchored map of transcriptional start sites in the model cyanobacterium Synechocystis sp. PCC6803. Proc. Natl Acad. Sci. USA 108, 2124–2129 (2011).

    Article  CAS  Google Scholar 

  13. Raghavan, R., Sloan, D. B. & Ochman, H. Antisense transcription is pervasive but rarely conserved in enteric bacteria. mBio 3, e00156–12 (2012).

    Article  CAS  Google Scholar 

  14. Lasa, I. et al. Genome-wide antisense transcription drives mRNA processing in bacteria. Proc. Natl Acad. Sci. USA 108, 20172–20177 (2011).

    Article  CAS  Google Scholar 

  15. Kawano, M., Storz, G., Rao, B. S., Rosner, J. L. & Martin, R. G. Detection of low-level promoter activity within open reading frame sequences of Escherichia coli. Nucleic Acids Res. 33, 6268–6276 (2005).

    Article  CAS  Google Scholar 

  16. Reppas, N. B., Wade, J. T., Church, G. M. & Struhl, K. The transition between transcriptional initiation and elongation in E. coli is highly variable and often rate limiting. Mol. Cell 24, 747–757 (2006).

    Article  CAS  Google Scholar 

  17. Wade, J. T. et al. Extensive functional overlap between sigma factors in Escherichia coli. Nature Struct. Mol. Biol. 13, 806–814 (2006).

    Article  CAS  Google Scholar 

  18. Mooney, R. A. et al. Regulator trafficking on bacterial transcription units in vivo. Mol. Cell 33, 97–108 (2009).

    Article  CAS  Google Scholar 

  19. Singh, S. S. et al. Widespread suppression of intragenic transcription initiation by H-NS. Genes Dev. 28, 214–219 (2014).

    Article  CAS  Google Scholar 

  20. Shimada, T., Yamazaki, Y., Tanaka, K. & Ishihama, A. The whole set of constitutive promoters recognized by RNA polymerase RpoD holoenzyme of Escherichia coli. PLoS ONE 9, e90447 (2014).

    Article  Google Scholar 

  21. Jensen, T. H., Jacquier, A. & Libri, D. Dealing with pervasive transcription. Mol. Cell 52, 473–484 (2013).

    Article  CAS  Google Scholar 

  22. Lee, D. J., Minchin, S. D. & Busby, S. J. Activating transcription in bacteria. Annu. Rev. Microbiol. 66, 125–152 (2012).

    Article  CAS  Google Scholar 

  23. Epshtein, V., Dutta, D., Wade, J. & Nudler, E. An allosteric mechanism of Rho-dependent transcription termination. Nature 463, 245–249 (2010).

    Article  CAS  Google Scholar 

  24. Ciampi, M. S. Rho-dependent terminators and transcription termination. Microbiology 152, 2515–2528 (2006).

    Article  CAS  Google Scholar 

  25. Singh, N. & Wade, J. T. Identification of regulatory RNA in bacterial genomes by genome-scale mapping of transcription start sites. Methods Mol. Biol. 1103, 1–10 (2014).

    Article  CAS  Google Scholar 

  26. Kim, D. et al. Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling. PLoS Genet. 8, e1002867 (2012).

    Article  CAS  Google Scholar 

  27. Cho, B. K., Kim, D., Knight, E. M., Zengler, K. & Palsson, B. O. Genome-scale reconstruction of the sigma factor network in Escherichia coli: topology and functional states. BMC Biol. 12, 4 (2014).

    Article  Google Scholar 

  28. Cho, B. K. et al. The transcription unit architecture of the Escherichia coli genome. Nature Biotech. 27, 1043–1049 (2009).

    Article  CAS  Google Scholar 

  29. Stringer, A. M. et al. Genome-scale analyses of Escherichia coli and Salmonella enterica AraC reveal noncanonical targets and an expanded core regulon. J. Bacteriol. 196, 660–671 (2014).

    Article  Google Scholar 

  30. Chen, Y. J. et al. Characterization of 582 natural and synthetic terminators and quantification of their design constraints. Nature Methods 10, 659–664 (2013).

    Article  CAS  Google Scholar 

  31. Nicolas, P. et al. Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science 335, 1103–1106 (2012).

    Article  CAS  Google Scholar 

  32. Leela, J. K., Syeda, A. H., Anupama, K. & Gowrishankar, J. Rho-dependent transcription termination is essential to prevent excessive genome-wide R-loops in Escherichia coli. Proc. Natl Acad. Sci. USA 110, 258–223 (2013).

    Article  CAS  Google Scholar 

  33. Gan, W. et al. R-loop-mediated genomic instability is caused by impairment of replication fork progression. Genes Dev. 25, 2041–2056 (2011).

    Article  CAS  Google Scholar 

  34. Dame, R. T., Noom, M. C. & Wuite, G. J. Bacterial chromatin organization by H-NS protein unravelled using dual DNA manipulation. Nature 444, 387–390 (2006).

    Article  CAS  Google Scholar 

  35. Peters, J. M. et al. Rho and NusG suppress pervasive antisense transcription in Escherichia coli. Genes Dev. 26, 2621–2633 (2012).

    Article  CAS  Google Scholar 

  36. Chandraprakash, D. & Seshasayee, A. S. Inhibition of factor-dependent transcription termination in Escherichia coli might relieve xenogene silencing by abrogating H-NS–DNA interactions in vivo. J. Biosci. 39, 53–61 (2014).

    Article  CAS  Google Scholar 

  37. Durand, S., Gilet, L. & Condon, C. The essential function of B. subtilis RNase III is to silence foreign toxin genes. PLoS Genet. 8, e1003181 (2012).

    Article  CAS  Google Scholar 

  38. Goldman, S. R. et al. NanoRNAs prime transcription initiation in vivo. Mol. Cell 42, 817–825 (2011).

    Article  CAS  Google Scholar 

  39. Panyukov, V. V. & Ozoline, O. N. Promoters of Escherichia coli versus promoter islands: function and structure comparison. PLoS ONE 8, e62601 (2013).

    Article  Google Scholar 

  40. Mercer, T. R. et al. The human mitochondrial transcriptome. Cell 146, 645–658 (2011).

    Article  CAS  Google Scholar 

  41. Shao, W., Price, M. N., Deutschbauer, A. M., Romine, M. F. & Arkin, A. P. Conservation of transcription start sites within genes across a bacterial genus. mBio 5, e01398–14 (2014).

    Article  Google Scholar 

  42. Lybecker, M., Zimmermann, B., Bilusic, I., Tukhtubaeva, N. & Schroeder, R. The double-stranded transcriptome of Escherichia coli. Proc. Natl Acad. Sci. USA 111, 3134–3139 (2014).

    Article  CAS  Google Scholar 

  43. Georg, J. & Hess, W. R. cis-antisense RNA, another level of gene regulation in bacteria. Microbiol. Mol. Biol. Rev. 75, 286–300 (2011).

    Article  CAS  Google Scholar 

  44. Brantl, S. & Wagner, E. G. An antisense RNA-mediated transcriptional attenuation mechanism functions in Escherichia coli. J. Bacteriol. 184, 2740–2747 (2002).

    Article  CAS  Google Scholar 

  45. Lasa, I., Toledo-Arana, A. & Gingeras, T. R. An effort to make sense of antisense transcription in bacteria. RNA Biol. 9, 1039–1044 (2012).

    Article  CAS  Google Scholar 

  46. Sesto, N., Wurtzel, O., Archambaud, C., Sorek, R. & Cossart, P. The excludon: a new concept in bacterial antisense RNA-mediated gene regulation. Nature Rev. Microbiol. 11, 75–82 (2013).

    Article  CAS  Google Scholar 

  47. Wurtzel, O. et al. Comparative transcriptomics of pathogenic and non-pathogenic Listeria species. Mol. Syst. Biol. 8, 583 (2012).

    Article  Google Scholar 

  48. Mutalik, V. K., Qi, L., Guimaraes, J. C., Lucks, J. B. & Arkin, A. P. Rationally designed families of orthogonal RNA regulators of translation. Nature Chem. Biol. 25, 447–454 (2012).

    Article  Google Scholar 

  49. Navarre, W. W. et al. Selective silencing of foreign DNA with low GC content by the H-NS protein in Salmonella. Science 313, 236–238 (2006).

    Article  CAS  Google Scholar 

  50. Martincorena, I., Seshasayee, A. S. & Luscombe, N. M. Evidence of non-random mutation rates suggests an evolutionary risk management strategy. Nature 485, 95–98 (2012).

    Article  CAS  Google Scholar 

  51. Epshtein, V. et al. UvrD facilitates DNA repair by pulling RNA polymerase backwards. Nature 505, 372–377 (2014).

    Article  CAS  Google Scholar 

  52. Savery, N. J. The molecular mechanism of transcription-coupled DNA repair. Trends Microbiol. 15, 326–333 (2007).

    Article  CAS  Google Scholar 

  53. Chao, Y., Papenfort, K., Reinhardt, R., Sharma, C. M. & Vogel, J. An atlas of Hfq-bound transcripts reveals 3′ UTRs as a genomic reservoir of regulatory small RNAs. EMBO J. 31, 4005–4019 (2012).

    Article  CAS  Google Scholar 

  54. Gibson, D. G. et al. Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329, 52–56 (2010).

    Article  CAS  Google Scholar 

  55. Wiser, M. J., Ribeck, N. & Lenski, R. E. Long-term dynamics of adaptation in asexual populations. Science. 342, 1364–1367 (2013).

    Article  CAS  Google Scholar 

  56. Herring, C. D. et al. Immobilization of Escherichia coli RNA polymerase and location of binding sites by use of chromatin immunoprecipitation and microarrays. J. Bacteriol. 187, 6166–6174 (2005).

    Article  CAS  Google Scholar 

  57. Grainger, D. C., Hurd, D., Harrison, M., Holdstock, J. & Busby, S. J. Studies of the distribution of Escherichia coli cAMP-receptor protein and RNA polymerase along the E. coli chromosome. Proc. Natl Acad. Sci. USA 102, 17693–17698 (2005).

    Article  CAS  Google Scholar 

  58. Streets, A. M. et al. Microfluidic single-cell whole-transcriptome sequencing. Proc. Natl Acad. Sci. USA 111, 7048–7053 (2014).

    Article  CAS  Google Scholar 

  59. Steuten, B. et al. Regulation of transcription by 6S RNAs: insights from the Escherichia coli and Bacillus subtilis model systems. RNA Biol. http://dx.doi.org/10.4161/rna.28827 (2014).

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

    Article  CAS  Google Scholar 

Download references

Acknowledgements

J.T.W. is funded by the National Institutes of Health Director's New Innovator Award DP2OD007188. D.C.G. thanks the Wellcome Trust for a Research Career Development Fellowship and the Leverhulme Trust for project grant RPG-2013-147.

Author information

Authors and Affiliations

  1. New York State Department of Health, and the Department of Biomedical Sciences, Wadsworth Center, Albany, New York 12208, USA, University at Albany-State University of New York, Albany, New York 12201, USA.,

    Joseph T. Wade

  2. Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    David C. Grainger

Authors
  1. Joseph T. Wade
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David C. Grainger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Joseph T. Wade or David C. Grainger.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wade, J., Grainger, D. Pervasive transcription: illuminating the dark matter of bacterial transcriptomes. Nat Rev Microbiol 12, 647–653 (2014). https://doi.org/10.1038/nrmicro3316

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro3316

This article is cited by

Search

Advanced 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