Over the past decade, bacterial small RNAs (sRNAs) have gone from a biological curiosity to being recognized as a major class of regulatory molecules. High-throughput methods for sampling the transcriptional output of bacterial cells demonstrate that sRNAs are universal features of bacterial transcriptomes, are plentiful, and appear to vary extensively over evolutionary time. With ever more bacteria coming under study, the question becomes how can we accelerate the discovery and functional characterization of sRNAs in diverse organisms. New technologies built on high-throughput sequencing are emerging that can rapidly provide global insight into the numbers and functions of sRNAs in bacteria of interest, providing information that can shape hypotheses and guide research. In this review, we describe recent developments in transcriptomics (RNA-seq) and functional genomics that we expect to help us develop an integrated, systems-level view of sRNA biology in bacteria.


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Literature Cited

  1. Altuvia S, Weinstein-Fischer D, Zhang A, Postow L, Storz G. 1.  1997. A small, stable RNA induced by oxidative stress: role as a pleiotropic regulator and antimutator. Cell 90:143–53 [Google Scholar]
  2. Argaman L, Hershberg R, Vogel J, Bejerano G, Wagner EGH. 2.  et al. 2001. Novel small RNA-encoding genes in the intergenic regions of Escherichia coli. Curr. Biol. 11:12941–50 [Google Scholar]
  3. Arnvig KB, Comas I, Thomson NR, Houghton J, Boshoff HI. 3.  et al. 2011. Sequence-based analysis uncovers an abundance of non-coding RNA in the total transcriptome of Mycobacterium tuberculosis. PLOS Pathog. 7:11e1002342 [Google Scholar]
  4. Artsimovitch I, Landick R. 4.  2002. The transcriptional regulator RfaH stimulates RNA chain synthesis after recruitment to elongation complexes by the exposed nontemplate DNA strand. Cell 109:2193–203 [Google Scholar]
  5. Ashton PM, Nair S, Dallman T, Rubino S, Rabsch W. 5.  et al. 2014. MinIon nanopore sequencing identifies the position and structure of a bacterial antibiotic resistance island. Nat. Biotechnol. 33:296–300 [Google Scholar]
  6. Bardill JP, Hammer BK. 6.  2012. Non-coding sRNAs regulate virulence in the bacterial pathogen Vibrio cholerae. RNA Biol. 9:4392–401 [Google Scholar]
  7. Barquist L, Boinett CJ, Cain AK. 7.  2013. Approaches to querying bacterial genomes with transposon-insertion sequencing. RNA Biol. 10:71161–69 [Google Scholar]
  8. Beisel CL, Storz G. 8.  2010. Base pairing small RNAs and their roles in global regulatory networks. FEMS Microbiol. Rev. 34:5866–82 [Google Scholar]
  9. Beisel CL, Updegrove TB, Janson BJ, Storz G. 9.  2012. Multiple factors dictate target selection by Hfq-binding small RNAs. EMBO J. 31:81961–74 [Google Scholar]
  10. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V. 10.  et al. 1997. The complete genome sequence of Escherichia coli K-12. Science 277:53311453–62 [Google Scholar]
  11. Bobrovskyy M, Vanderpool CK. 11.  2013. Regulation of bacterial metabolism by small RNAs using diverse mechanisms. Annu. Rev. Genet. 47:209–32 [Google Scholar]
  12. Boisset S, Geissmann T, Huntzinger E, Fechter P, Bendridi N. 12.  et al. 2007. Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator rot by an antisense mechanism. Genes Dev. 21:111353–66 [Google Scholar]
  13. Bordbar A, Monk JM, King ZA, Palsson BO. 13.  2014. Constraint-based models predict metabolic and associated cellular functions. Nat. Rev. Genet. 15:2107–20 [Google Scholar]
  14. Bossi L, Figueroa-Bossi N. 14.  2007. A small RNA downregulates LamB maltoporin in Salmonella. Mol. Microbiol. 65:3799–810 [Google Scholar]
  15. Bossi L, Schwartz A, Guillemardet B, Boudvillain M, Figueroa-Bossi N. 15.  2012. A role for Rho-dependent polarity in gene regulation by a noncoding small RNA. Genes Dev. 26:161864–73 [Google Scholar]
  16. Brantl S, Brückner R. 16.  2014. Small regulatory RNAs from low-GC Gram-positive bacteria. RNA Biol. 11:5443–56 [Google Scholar]
  17. Brouwer RWW, Kuipers OP, van Hijum SAFT. 17.  2008. The relative value of operon predictions. Brief. Bioinform. 9:5367–75 [Google Scholar]
  18. Brownlee GG. 18.  1971. Sequence of 6S RNA of E. coli. Nature 229:5147–49 [Google Scholar]
  19. Bryant J, Chewapreecha C, Bentley SD. 19.  2012. Developing insights into the mechanisms of evolution of bacterial pathogens from whole-genome sequences. Future Microbiol. 7:111283–96 [Google Scholar]
  20. Busch A, Richter AS, Backofen R. 20.  2008. IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions. Bioinformatics 24:242849–56 [Google Scholar]
  21. Caldelari I, Chao Y, Romby P, Vogel J. 21.  2013. RNA-mediated regulation in pathogenic bacteria. Cold Spring Harb. Perspect. Med. 3:9a010298 [Google Scholar]
  22. Cambray G, Guimaraes JC, Mutalik VK, Lam C, Mai Q-A. 22.  et al. 2013. Measurement and modeling of intrinsic transcription terminators. Nucleic Acids Res. 41:95139–48 [Google Scholar]
  23. Caron M-P, Lafontaine DA, Massé E. 23.  2010. Small RNA–mediated regulation at the level of transcript stability. RNA Biol. 7:2140–44 [Google Scholar]
  24. Chao Y, Papenfort K, Reinhardt R, Vogel J. 24.  2012. An atlas of Hfq-bound transcripts reveals 3′ UTRs as a genomic reservoir of regulatory small RNAs. EMBO J. 31:204005–19 [Google Scholar]
  25. Chao Y, Vogel J. 25.  2010. The role of Hfq in bacterial pathogens. Curr. Opin. Microbiol. 13:124–33 [Google Scholar]
  26. Chaudhuri RR, Morgan E, Peters SE, Pleasance SJ, Hudson DL. 26.  et al. 2013. Comprehensive assignment of roles for Salmonella Typhimurium genes in intestinal colonization of food-producing animals. PLOS Genet. 9:4e1003456 [Google Scholar]
  27. Chaudhuri RR, Peters SE, Pleasance SJ, Northen H, Willers C. 27.  et al. 2009. Comprehensive identification of Salmonella enterica serovar Typhimurium genes required for infection of BALB/c mice. PLOS Pathog. 5:7e1000529 [Google Scholar]
  28. Chen Y-J, Liu P, Nielsen AAK, Brophy JAN, Clancy K. 28.  et al. 2013. Characterization of 582 natural and synthetic terminators and quantification of their design constraints. Nat. Methods 10:7659–64 [Google Scholar]
  29. Cho B-K, Zengler K, Qiu Y, Park YS, Knight EM. 29.  et al. 2009. The transcription unit architecture of the Escherichia coli genome. Nat. Biotechnol. 27:111043–49 [Google Scholar]
  30. Conway T, Creecy JP, Maddox SM, Grissom JE, Conkle TL. 30.  et al. 2014. Unprecedented high-resolution view of bacterial operon architecture revealed by RNA sequencing. mBio 5:4e01442–14 [Google Scholar]
  31. Corcoran CP, Podkaminski D, Papenfort K, Urban JH, Hinton JCD, Vogel J. 31.  2012. Superfolder GFP reporters validate diverse new mRNA targets of the classic porin regulator, MicF RNA. Mol. Microbiol. 84:3428–45 [Google Scholar]
  32. Creecy JP, Conway T. 32.  2014. Quantitative bacterial transcriptomics with RNA-seq. Curr. Opin. Microbiol. 23:133–40 [Google Scholar]
  33. Croucher NJ, Didelot X. 33.  2014. The application of genomics to tracing bacterial pathogen transmission. Curr. Opin. Microbiol. 23:62–67 [Google Scholar]
  34. Croucher NJ, Thomson NR. 34.  2010. Studying bacterial transcriptomes using RNA-seq. Curr. Opin. Microbiol. 13:5619–24 [Google Scholar]
  35. Curtis MM, Hu Z, Klimko C, Narayanan S, Deberardinis R, Sperandio V. 35.  2014. The gut commensal Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape. Cell Host Microbe 16:6759–69 [Google Scholar]
  36. Darnell RB. 36.  2010. HITS-CLIP: panoramic views of protein-RNA regulation in living cells. Wiley Interdiscip. Rev. RNA 1:2266–86 [Google Scholar]
  37. De Lay N, Schu DJ, Gottesman S. 37.  2013. Bacterial small RNA–based negative regulation: Hfq and its accomplices. J. Biol. Chem. 288:127996–8003 [Google Scholar]
  38. Desnoyers G, Morissette A, Prévost K, Massé E. 38.  2009. Small RNA–induced differential degradation of the polycistronic mRNA iscRSUA. EMBO J. 28:111551–61 [Google Scholar]
  39. Dimastrogiovanni D, Fröhlich KS, Bandyra KJ, Bruce HA, Hohensee S. 39.  et al. 2014. Recognition of the small regulatory RNA RydC by the bacterial Hfq protein. eLife doi:10.7554/eLife.05375
  40. Dugar G, Herbig A, Förstner KU, Heidrich N, Reinhardt R. 40.  et al. 2013. High-resolution transcriptome maps reveal strain-specific regulatory features of multiple Campylobacter jejuni isolates. PLOS Genet. 9:5e1003495 [Google Scholar]
  41. Durand S, Braun F, Lioliou E, Romilly C, Helfer A-C. 41.  et al. 2015. A nitric oxide regulated small RNA controls expression of genes involved in redox homeostasis in Bacillus subtilis. PLOS Genet. 11:2e1004957 [Google Scholar]
  42. Eddy SR. 42.  2014. Computational analysis of conserved RNA secondary structure in transcriptomes and genomes. Annu. Rev. Biophys. 43:433–56 [Google Scholar]
  43. Eggenhofer F, Tafer H, Stadler PF, Hofacker IL. 43.  2011. RNApredator: fast accessibility-based prediction of sRNA targets. Nucleic Acids Res. 39:W149–54 [Google Scholar]
  44. Engreitz JM, Sirokman K, McDonel P, Shishkin AA, Surka C. 44.  et al. 2014. RNA-RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell 159:1188–99 [Google Scholar]
  45. Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG. 45.  2002. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). PNAS 99:117687–92 [Google Scholar]
  46. Feaga HA, Viollier PH, Keiler KC. 46.  2014. Release of nonstop ribosomes is essential. mBio 5:6e01916 [Google Scholar]
  47. Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA. 47.  2012. Invasive non-typhoidal Salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 379:98352489–99 [Google Scholar]
  48. Feng L, Rutherford ST, Papenfort K, Bagert JD, van Kessel JC. 48.  et al. 2015. A Qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics. Cell 160:1–2228–40 [Google Scholar]
  49. Ferreyra JA, Wu KJ, Hryckowian AJ, Bouley DM, Weimer BC, Sonnenburg JL. 49.  2014. Gut microbiota–produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance. Cell Host Microbe 16:6770–77 [Google Scholar]
  50. Fields PI, Swanson RV, Haidaris CG, Heffron F. 50.  1986. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. PNAS 83:145189–93 [Google Scholar]
  51. Figueroa-Bossi N, Valentini M, Malleret L, Fiorini F, Bossi L. 51.  2009. Caught at its own game: regulatory small RNA inactivated by an inducible transcript mimicking its target. Genes Dev. 23:172004–15 [Google Scholar]
  52. Friedersdorf MB, Keene JD. 52.  2014. Advancing the functional utility of PAR-CLIP by quantifying background binding to mRNAs and lncRNAs. Genome Biol. 15:1R2 [Google Scholar]
  53. Fröhlich KS, Papenfort K, Fekete A, Vogel J. 53.  2013. A small RNA activates CFA synthase by isoform-specific mRNA stabilization. EMBO J. 32:222963–79 [Google Scholar]
  54. Fröhlich KS, Vogel J. 54.  2009. Activation of gene expression by small RNA. Curr. Opin. Microbiol. 12:6674–82 [Google Scholar]
  55. Gardner PP, Barquist L, Bateman A, Nawrocki EP, Weinberg Z. 55.  2011. RNIE: genome-wide prediction of bacterial intrinsic terminators. Nucleic Acids Res. 39:145845–52 [Google Scholar]
  56. Gong H, Vu G-P, Bai Y, Chan E, Wu R. 56.  et al. 2011. A Salmonella small non-coding RNA facilitates bacterial invasion and intracellular replication by modulating the expression of virulence factors. PLOS Pathog. 7:9e1002120 [Google Scholar]
  57. Gosai SJ, Foley SW, Wang D, Silverman IM, Selamoglu N. 57.  et al. 2015. Global analysis of the RNA-protein interaction and RNA secondary structure landscapes of the Arabidopsis nucleus. Mol. Cell 57:2376–88 [Google Scholar]
  58. Gottesman S. 58.  2004. The small RNA regulators of Escherichia coli: roles and mechanisms. Annu. Rev. Microbiol. 58:303–28 [Google Scholar]
  59. Gottesman S, Storz G. 59.  2011. Bacterial small RNA regulators: versatile roles and rapidly evolving variations. Cold Spring Harb. Perspect. Biol. 3:12 pii:a003798 [Google Scholar]
  60. Grant AJ, Restif O, McKinley TJ, Sheppard M, Maskell DJ, Mastroeni P. 60.  2008. Modelling within-host spatiotemporal dynamics of invasive bacterial disease. PLOS Biol. 6:4e74 [Google Scholar]
  61. Gripenland J, Netterling S, Loh E, Tiensuu T, Toledo-Arana A, Johansson J. 61.  2010. RNAs: regulators of bacterial virulence. Nat. Rev. Microbiol. 8:12857–66 [Google Scholar]
  62. Grosswendt S, Filipchyk A, Manzano M, Klironomos F, Schilling M. 62.  et al. 2014. Unambiguous identification of miRNA:target site interactions by different types of ligation reactions. Mol. Cell 54:61042–54 [Google Scholar]
  63. Güell M, van Noort V, Yus E, Chen W-H, Leigh-Bell J. 63.  et al. 2009. Transcriptome complexity in a genome-reduced bacterium. Science 326:59571268–71 [Google Scholar]
  64. Güell M, Yus E, Lluch-Senar M, Serrano L. 64.  2011. Bacterial transcriptomics: What is beyond the RNA horiz-ome?. Nat. Rev. Microbiol. 9:9658–69 [Google Scholar]
  65. Guo MS, Updegrove TB, Gogol EB, Shabalina SA, Gross CA, Storz G. 65.  2014. MicL, a new σE-dependent sRNA, combats envelope stress by repressing synthesis of Lpp, the major outer membrane lipoprotein. Genes Dev. 28:141620–34 [Google Scholar]
  66. Guttman M, Garber M, Levin JZ, Donaghey J, Robinson J. 66.  et al. 2010. Ab initio reconstruction of cell type–specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nat. Biotechnol. 28:5503–10 [Google Scholar]
  67. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J. 67.  et al. 2010. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141:1129–41 [Google Scholar]
  68. Hammann P, Parmentier D, Cerciat M, Reimegård J, Helfer A-C. 68.  et al. 2014. A method to map changes in bacterial surface composition induced by regulatory RNAs in Escherichia coli and Staphylococcus aureus. Biochimie 106:175–79 [Google Scholar]
  69. Hammarlöf DL, Canals R, Hinton JCD. 69.  2013. The fun of identifying gene function in bacterial pathogens; insights from Salmonella functional genomics. Curr. Opin. Microbiol. 16:5643–51 [Google Scholar]
  70. Hansen AK, Degnan PH. 70.  2014. Widespread expression of conserved small RNAs in small symbiont genomes. ISME J. 8:122490–502 [Google Scholar]
  71. He M, Miyajima F, Roberts P, Ellison L, Pickard DJ. 71.  et al. 2013. Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nat. Genet. 45:1109–13 [Google Scholar]
  72. Hébrard M, Kröger C, Srikumar S, Colgan A, Händler K, Hinton JCD. 72.  2012. sRNAs and the virulence of Salmonella enterica serovar Typhimurium. RNA Biol. 9:4437–45 [Google Scholar]
  73. Helwak A, Kudla G, Dudnakova T, Tollervey D. 73.  2013. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153:3654–65 [Google Scholar]
  74. Hershberg R, Altuvia S, Margalit H. 74.  2003. A survey of small RNA-encoding genes in Escherichia coli. Nucleic Acids Res. 31:71813–20 [Google Scholar]
  75. Hess WR, Berghoff BA, Wilde A, Steglich C, Klug G. 75.  2014. Riboregulators and the role of Hfq in photosynthetic bacteria. RNA Biol. 11:5413–26 [Google Scholar]
  76. Holmqvist E, Reimegård J, Sterk M, Grantcharova N, Römling U, Wagner EGH. 76.  2010. Two antisense RNAs target the transcriptional regulator CsgD to inhibit curli synthesis. EMBO J. 29:111840–50 [Google Scholar]
  77. Holmqvist E, Reimegård J, Wagner EGH. 77.  2013. Massive functional mapping of a 5′-UTR by saturation mutagenesis, phenotypic sorting and deep sequencing. Nucleic Acids Res. 41:12e122 [Google Scholar]
  78. Holmqvist E, Unoson C, Reimegård J, Wagner EGH. 78.  2012. A mixed double negative feedback loop between the sRNA MicF and the global regulator Lrp. Mol. Microbiol. 84:3414–27 [Google Scholar]
  79. Hussein R, Lim HN. 79.  2011. Disruption of small RNA signaling caused by competition for Hfq. PNAS 108:31110–15 [Google Scholar]
  80. Ingolia NT. 80.  2014. Ribosome profiling: new views of translation, from single codons to genome scale. Nat. Rev. Genet. 15:3205–13 [Google Scholar]
  81. Ingolia NT, Ghaemmaghami S, Newman JRS, Weissman JS. 81.  2009. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324:5924218–23 [Google Scholar]
  82. Katz Y, Wang ET, Airoldi EM, Burge CB. 82.  2010. Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nat. Methods 7:121009–15 [Google Scholar]
  83. Kim D, Hong JS-J, Qiu Y, Nagarajan H, Seo J-H. 83.  et al. 2012. Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling. PLOS Genet. 8:8e1002867 [Google Scholar]
  84. König J, Zarnack K, Luscombe NM, Ule J. 84.  2012. Protein-RNA interactions: new genomic technologies and perspectives. Nat. Rev. Genet. 13:277–83 [Google Scholar]
  85. König J, Zarnack K, Rot G, Curk T, Kayikci M. 85.  et al. 2010. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct. Mol. Biol. 17:7909–15 [Google Scholar]
  86. Koren S, Phillippy AM. 86.  2015. One chromosome, one contig: complete microbial genomes from long-read sequencing and assembly. Curr. Opin. Microbiol. 23:110–20 [Google Scholar]
  87. Kröger C, Colgan A, Srikumar S, Händler K, Sivasankaran SK. 87.  et al. 2013. An infection-relevant transcriptomic compendium for Salmonella enterica serovar Typhimurium. Cell Host Microbe 14:6683–95 [Google Scholar]
  88. Kröger C, Dillon SC, Cameron ADS, Papenfort K, Sivasankaran SK. 88.  et al. 2012. The transcriptional landscape and small RNAs of Salmonella enterica serovar Typhimurium. PNAS 109:20E1277–86 [Google Scholar]
  89. Kudla G, Granneman S, Hahn D, Beggs JD, Tollervey D. 89.  2011. Cross-linking, ligation, and sequencing of hybrids reveals RNA-RNA interactions in yeast. PNAS 108:2410010–15 [Google Scholar]
  90. Lalaouna D, Carrier M-C, Semsey S, Brouard J-S, Wang J, Wade JT, Massé E. 90.  2015. A 3 external transcribed spacer in a tRNA transcript acts as a sponge for small RNAs to prevent transcriptional noise. Mol. Cell. 58:3393–405 [Google Scholar]
  91. Langridge GC, Phan M-D, Turner DJ, Perkins TT, Parts L. 91.  et al. 2009. Simultaneous assay of every Salmonella Typhi gene using one million transposon mutants. Genome Res. 19:122308–16 [Google Scholar]
  92. Law CW, Chen Y, Shi W, Smyth GK. 92.  2014. Voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15:2R29 [Google Scholar]
  93. Lease RA, Cusick ME, Belfort M. 93.  1998. Riboregulation in Escherichia coli: DsrA RNA acts by RNA:RNA interactions at multiple loci. PNAS 95:2112456–61 [Google Scholar]
  94. Lenz DH, Mok KC, Lilley BN, Kulkarni RV, Wingreen NS, Bassler BL. 94.  2004. The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell. 118:169–82 [Google Scholar]
  95. Li G-W, Oh E, Weissman JS. 95.  2012. The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria. Nature 484:7395538–41 [Google Scholar]
  96. Lindgreen S, Umu SU, Lai AS-W, Eldai H, Liu W. 96.  et al. 2014. Robust identification of noncoding RNA from transcriptomes requires phylogenetically-informed sampling. PLOS Comput. Biol. 10:10e1003907 [Google Scholar]
  97. Livny J, Waldor MK. 97.  2007. Identification of small RNAs in diverse bacterial species. Curr. Opin. Microbiol. 10:296–101 [Google Scholar]
  98. Loman NJ, Constantinidou C, Chan JZM, Halachev M, Sergeant M. 98.  et al. 2012. High-throughput bacterial genome sequencing: an embarrassment of choice, a world of opportunity. Nat. Rev. Microbiol. 10:9599–606 [Google Scholar]
  99. Love M, Huber W, Anders S. 99.  2014. Moderated estimation of fold change and dispersion for RNA-seq data with DEseq2. Genome Biol. 15:12550 [Google Scholar]
  100. Mandin P, Gottesman S. 100.  2009. A genetic approach for finding small RNA regulators of genes of interest identifies RybC as regulating the DpiA/DpiB two-component system. Mol. Microbiol. 72:3551–65 [Google Scholar]
  101. Mann B, van Opijnen T, Wang J, Obert C, Wang Y-D. 101.  et al. 2012. Control of virulence by small RNAs in Streptococcus pneumoniae. PLOS Pathog. 8:7e1002788 [Google Scholar]
  102. Martin J, Zhu W, Passalacqua KD, Bergman N, Borodovsky M. 102.  2010. Bacillus anthracis genome organization in light of whole transcriptome sequencing. BMC Bioinform. 11:Suppl. 3S10 [Google Scholar]
  103. Massé E, Vanderpool CK, Gottesman S. 103.  2005. Effect of RyhB small RNA on global iron use in Escherichia coli. J. Bacteriol. 187:206962–71 [Google Scholar]
  104. Mastroeni P, Grant A, Restif O, Maskell D. 104.  2009. A dynamic view of the spread and intracellular distribution of Salmonella enterica. Nat. Rev. Microbiol. 7:173–80 [Google Scholar]
  105. Mazurkiewicz P, Tang CM, Boone C, Holden DW. 105.  2006. Signature-tagged mutagenesis: barcoding mutants for genome-wide screens. Nat. Rev. Genet. 7:12929–39 [Google Scholar]
  106. McAdam PR, Richardson EJ, Fitzgerald JR. 106.  2014. High-throughput sequencing for the study of bacterial pathogen biology. Curr. Opin. Microbiol. 19:106–13 [Google Scholar]
  107. McCarthy DJ, Chen Y, Smyth GK. 107.  2012. Differential expression analysis of multifactor RNA-seq experiments with respect to biological variation. Nucleic Acids Res. 40:104288–97 [Google Scholar]
  108. McClelland M, Sanderson KE, Spieth J, Clifton SW, Latreille P. 108.  et al. 2001. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:6858852–56 [Google Scholar]
  109. McClure R, Balasubramanian D, Sun Y, Bobrovskyy M, Sumby P. 109.  et al. 2013. Computational analysis of bacterial RNA-seq data. Nucleic Acids Res. 41:14e140 [Google Scholar]
  110. McHugh CA, Russell P, Guttman M. 110.  2014. Methods for comprehensive experimental identification of RNA-protein interactions. Genome Biol. 15:1203 [Google Scholar]
  111. Mellin JR, Cossart P. 111.  2012. The non-coding RNA world of the bacterial pathogen Listeria monocytogenes. RNA Biol. 9:4372–78 [Google Scholar]
  112. Mendoza-Vargas A, Olvera L, Olvera M, Grande R, Vega-Alvarado L. 112.  et al. 2009. Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli. PLOS ONE 4:10e7526 [Google Scholar]
  113. Michaux C, Verneuil N, Hartke A, Giard J-C. 113.  2014. Physiological roles of small RNA molecules. Microbiology 160:Pt. 61007–19 [Google Scholar]
  114. Mika F, Hengge R. 114.  2014. Small RNAs in the control of RpoS, CsgD, and biofilm architecture of Escherichia coli. RNA Biol. 11:5494–507 [Google Scholar]
  115. Milek M, Wyler E, Landthaler M. 115.  2012. Transcriptome-wide analysis of protein-RNA interactions using high-throughput sequencing. Semin. Cell Dev. Biol. 23:2206–12 [Google Scholar]
  116. Mili S, Steitz JA. 116.  2004. Evidence for reassociation of RNA-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses. RNA 10:111692–94 [Google Scholar]
  117. Miyakoshi M, Chao Y, Vogel J. 117.  2015. Cross talk between ABC transporter mRNAs via a target mRNA-derived sponge of the GcvB small RNA. EMBO J. 34:111478–92 [Google Scholar]
  118. Miyakoshi M, Chao Y, Vogel J. 118.  2015. Regulatory small RNAs from the 3′ regions of bacterial mRNAs. Curr. Opin. Microbiol. 24:132–39 [Google Scholar]
  119. Mizuno T, Chou MY, Inouye M. 119.  1984. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). PNAS 81:71966–70 [Google Scholar]
  120. Modi SR, Camacho DM, Kohanski MA, Walker GC, Collins JJ. 120.  2011. Functional characterization of bacterial sRNAs using a network biology approach. PNAS 108:3715522–27 [Google Scholar]
  121. Møller T, Franch T, Højrup P, Keene DR, Bächinger HP. 121.  et al. 2002. Hfq: a bacterial Sm-like protein that mediates RNA-RNA interaction. Mol. Cell 9:123–30 [Google Scholar]
  122. Moon K, Gottesman S. 122.  2011. Competition among Hfq-binding small RNAs in Escherichia coli. Mol. Microbiol. 82:61545–62 [Google Scholar]
  123. Morita T, Maki K, Aiba H. 123.  2005. RNase E-based ribonucleoprotein complexes: mechanical basis of mRNA destabilization mediated by bacterial noncoding RNAs. Genes Dev. 19:182176–86 [Google Scholar]
  124. Moxon R, Bayliss C, Hood D. 124.  2006. Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu. Rev. Genet. 40:307–33 [Google Scholar]
  125. 125. Nature 2014. The digital toolbox. Nature 513:75166 [Google Scholar]
  126. 126. Nat. Methods 2013. Matters of significance. Nat. Methods 10:9805 [Google Scholar]
  127. Ng W-L, Bassler BL. 127.  2009. Bacterial quorum-sensing network architectures. Annu. Rev. Genet. 43:197–222 [Google Scholar]
  128. Nichols RJ, Sen S, Choo YJ, Beltrao P, Zietek M. 128.  et al. 2011. Phenotypic landscape of a bacterial cell. Cell 144:1143–56 [Google Scholar]
  129. Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S. 129.  1993. Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J. 12:103967–75 [Google Scholar]
  130. Oglesby-Sherrouse AG, Murphy ER. 130.  2013. Iron-responsive bacterial small RNAs: variations on a theme. Metallomics 5:4276–86 [Google Scholar]
  131. Oh E, Becker AH, Sandikci A, Huber D, Chaba R. 131.  et al. 2011. Selective ribosome profiling reveals the cotranslational chaperone action of trigger factor in vivo. Cell 147:61295–308 [Google Scholar]
  132. Okoro CK, Kingsley RA, Connor TR, Harris SR, Parry CM. 132.  et al. 2012. Intracontinental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa. Nat. Genet. 44:111215–21 [Google Scholar]
  133. Overgaard M, Johansen J, Møller-Jensen J, Valentin-Hansen P. 133.  2009. Switching off small RNA regulation with trap-mRNA. Mol. Microbiol. 73:5790–800 [Google Scholar]
  134. Padalon-Brauch G, Hershberg R, Elgrably-Weiss M, Baruch K, Rosenshine I. 134.  et al. 2008. Small RNAs encoded within genetic islands of Salmonella Typhimurium show host-induced expression and role in virulence. Nucleic Acids Res. 36:61913–27 [Google Scholar]
  135. Pain A, Ott A, Amine H, Rochet T, Bouloc P, Gauthret D. 135.  2015. An assessment of bacterial small RNA target prediction programs. RNA Biol. 12:5509–13 [Google Scholar]
  136. Papenfort K, Bouvier M, Mika F, Sharma CM, Vogel J. 136.  2010. Evidence for an autonomous 5′ target recognition domain in an Hfq-associated small RNA. PNAS 107:4720435–40 [Google Scholar]
  137. Papenfort K, Pfeiffer V, Mika F, Lucchini S, Hinton JCD, Vogel J. 137.  2006. σE-dependent small RNAs of salmonella respond to membrane stress by accelerating global omp mRNA decay. Mol. Microbiol. 62:61674–88 [Google Scholar]
  138. Papenfort K, Said N, Welsink T, Lucchini S, Hinton JCD, Vogel J. 138.  2009. Specific and pleiotropic patterns of mRNA regulation by ArcZ, a conserved, Hfq-dependent small RNA. Mol. Microbiol. 74:1139–58 [Google Scholar]
  139. Papenfort K, Sun Y, Miyakoshi M, Vanderpool CK, Vogel J. 139.  2013. Small RNA–mediated activation of sugar phosphatase mRNA regulates glucose homeostasis. Cell 153:2426–37 [Google Scholar]
  140. Papenfort K, Vogel J. 140.  2014. Small RNA functions in carbon metabolism and virulence of enteric pathogens. Front. Cell. Infect. Microbiol. 4:91 [Google Scholar]
  141. Parkhill J, Dougan G, James KD, Thomson NR, Pickard D. 141.  et al. 2001. Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413:6858848–52 [Google Scholar]
  142. Peer A, Margalit H. 142.  2011. Accessibility and evolutionary conservation mark bacterial small-RNA target-binding regions. J. Bacteriol. 193:71690–701 [Google Scholar]
  143. Peer A, Margalit H. 143.  2014. Evolutionary patterns of Escherichia coli small RNAs and their regulatory interactions. RNA 20:7994–1003 [Google Scholar]
  144. Peng Y, Curtis JE, Fang X, Woodson SA. 144.  2014. Structural model of an mRNA in complex with the bacterial chaperone Hfq. PNAS 111:4817134–39 [Google Scholar]
  145. Pernitzsch SR, Tirier SM, Beier D, Sharma CM. 145.  2014. A variable homopolymeric G-repeat defines small RNA–mediated posttranscriptional regulation of a chemotaxis receptor in Helicobacter pylori. PNAS 111:4E501–10 [Google Scholar]
  146. Peterman N, Lavi-Itzkovitz A, Levine E. 146.  2014. Large-scale mapping of sequence-function relations in small regulatory RNAs reveals plasticity and modularity. Nucleic Acids Res. 42:1912177–88 [Google Scholar]
  147. Peters JM, Vangeloff AD, Landick R. 147.  2011. Bacterial transcription terminators: the RNA 3′-end chronicles. J. Mol. Biol. 412:5793–813 [Google Scholar]
  148. Pfeiffer V, Sittka A, Tomer R, Tedin K, Brinkmann V, Vogel J. 148.  2007. A small non-coding RNA of the invasion gene island (SPI-1) represses outer membrane protein synthesis from the Salmonella core genome. Mol. Microbiol. 66:51174–91 [Google Scholar]
  149. Pham TAN, Clare S, Goulding D, Arasteh JM, Stares MD. 149.  et al. 2014. Epithelial il-22ra1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen. Cell Host Microbe 16:4504–16 [Google Scholar]
  150. Pham TAN, Lawley TD. 150.  2014. Emerging insights on intestinal dysbiosis during bacterial infections. Curr. Opin. Microbiol. 17:67–74 [Google Scholar]
  151. Pichon C, Felden B. 151.  2005. Small RNA genes expressed from Staphylococcus aureus genomic and pathogenicity islands with specific expression among pathogenic strains. PNAS 102:4014249–54 [Google Scholar]
  152. Quail MA, Smith M, Coupland P, Otto TD, Harris SR. 152.  et al. 2012. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genomics 13:341 [Google Scholar]
  153. Quick J, Quinlan AR, Loman NJ. 153.  2014. A reference bacterial genome dataset generated on the MinIonTM portable single-molecule nanopore sequencer. GigaScience 3:22 [Google Scholar]
  154. Rabani M, Raychowdhury R, Jovanovic M, Rooney M, Stumpo DJ. 154.  et al. 2014. High-resolution sequencing and modeling identifies distinct dynamic RNA regulatory strategies. Cell 159:71698–710 [Google Scholar]
  155. Raghavan R, Groisman EA, Ochman H. 155.  2011. Genome-wide detection of novel regulatory RNAs in E. coli. Genome Res. 21:91487–97 [Google Scholar]
  156. Rasmussen AA, Eriksen M, Gilany K, Udesen C, Franch T. 156.  et al. 2005. Regulation of OmpA mRNA stability: the role of a small regulatory RNA in growth phase–dependent control. Mol. Microbiol. 58:51421–29 [Google Scholar]
  157. Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS. 157.  et al. 2013. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499:7457172–77 [Google Scholar]
  158. Richter AS, Backofen R. 158.  2012. Accessibility and conservation: general features of bacterial small RNA–mRNA interactions?. RNA Biol. 9:7954–65 [Google Scholar]
  159. Riley KJ, Steitz JA. 159.  2013. The “observer effect” in genome-wide surveys of protein-RNA interactions. Mol. Cell 49:4601–4 [Google Scholar]
  160. Rivas E, Klein RJ, Jones TA, Eddy SR. 160.  2001. Computational identification of noncoding RNAs in E. coli by comparative genomics. Curr. Biol. 11:171369–73 [Google Scholar]
  161. Romilly C, Caldelari I, Parmentier D, Lioliou E, Romby P, Fechter P. 161.  2012. Current knowledge on regulatory RNAs and their machineries in Staphylococcus aureus. RNA Biol. 9:4402–13 [Google Scholar]
  162. Sahagan BG, Dahlberg JE. 162.  1979. A small, unstable RNA molecule of Escherichia coli: spot 42 RNA: I. nucleotide sequence analysis. J. Mol. Biol. 131:3573–92 [Google Scholar]
  163. Saliba A-E, Westermann AJ, Gorski SA, Vogel J. 163.  2014. Single-cell RNA-seq: advances and future challenges. Nucleic Acids Res. 42:148845–60 [Google Scholar]
  164. Salzberg SL, Phillippy AM, Zimin A, Puiu D, Magoc T. 164.  et al. 2012. GAGE: a critical evaluation of genome assemblies and assembly algorithms. Genome Res. 22:3557–67 [Google Scholar]
  165. Santiviago CA, Reynolds MM, Porwollik S, Choi S-H, Long F. 165.  et al. 2009. Analysis of pools of targeted Salmonella deletion mutants identifies novel genes affecting fitness during competitive infection in mice. PLOS Pathog. 5:7e1000477 [Google Scholar]
  166. Santos RL, Zhang S, Tsolis RM, Kingsley RA, Adams LG, Bäumler AJ. 166.  2001. Animal models of Salmonella infections: enteritis versus typhoid fever. Microbes Infect. 3:14–151335–44 [Google Scholar]
  167. Schrader JM, Zhou B, Li G-W, Lasker K, Childers WS. 167.  et al. 2014. The coding and noncoding architecture of the Caulobacter crescentus genome. PLOS Genet. 10:7e1004463 [Google Scholar]
  168. Sharma CM, Darfeuille F, Plantinga TH, Vogel J. 168.  2007. A small RNA regulates multiple ABC transporter mRNAs by targeting C/A-rich elements inside and upstream of ribosome-binding sites. Genes Dev. 21:212804–17 [Google Scholar]
  169. Sharma CM, Hoffmann S, Darfeuille F, Reignier J, Findeiss S. 169.  et al. 2010. The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464:7286250–55 [Google Scholar]
  170. Sharma CM, Vogel J. 170.  2009. Experimental approaches for the discovery and characterization of regulatory small RNA. Curr. Opin. Microbiol. 12:5536–46 [Google Scholar]
  171. Sharma CM, Vogel J. 171.  2014. Differential RNA-seq: the approach behind and the biological insight gained. Curr. Opin. Microbiol. 19:97–105 [Google Scholar]
  172. Silverman IM, Li F, Alexander A, Goff L, Trapnell C. 172.  et al. 2014. RNase-mediated protein footprint sequencing reveals protein-binding sites throughout the human transcriptome. Genome Biol. 15:1R3 [Google Scholar]
  173. Singh N, Wade JT. 173.  2014. Identification of regulatory RNA in bacterial genomes by genome-scale mapping of transcription start sites. Methods Mol. Biol. 1103:1–10 [Google Scholar]
  174. Sittka A, Lucchini S, Papenfort K, Sharma CM, Rolle K. 174.  et al. 2008. Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator, Hfq. PLOS Genet. 4:8e1000163 [Google Scholar]
  175. Sorek R, Cossart P. 175.  2010. Prokaryotic transcriptomics: a new view on regulation, physiology and pathogenicity. Nat. Rev. Genet. 11:19–16 [Google Scholar]
  176. Stevens MP, Humphrey TJ, Maskell DJ. 176.  2009. Molecular insights into farm animal and zoonotic Salmonella infections. Philos. Trans. R. Soc. Lond. B 364:15302709–23 [Google Scholar]
  177. Storz G, Gottesman S. 177.  2015. RNA reflections: converging on Hfq. RNA 21:511–512 [Google Scholar]
  178. Stringer AM, Currenti S, Bonocora RP, Baranowski C, Petrone BL. 178.  et al. 2014. Genome-scale analyses of Escherichia coli and Salmonella enterica AraC reveal noncanonical targets and an expanded core regulon. J. Bacteriol. 196:3660–71 [Google Scholar]
  179. Temkin E, Adler A, Lerner A, Carmeli Y. 179.  2014. Carbapenem-resistant Enterobacteriaceae: biology, epidemiology, and management. Ann. N. Y. Acad. Sci.132322–42
  180. Tjaden B, Goodwin SS, Opdyke JA, Guillier M, Fu DX. 180.  et al. 2006. Target prediction for small, noncoding RNAs in bacteria. Nucleic Acids Res. 34:92791–802 [Google Scholar]
  181. Tjaden B, Saxena RM, Stolyar S, Haynor DR, Kolker E, Rosenow C. 181.  2002. Transcriptome analysis of Escherichia coli using high-density oligonucleotide probe arrays. Nucleic Acids Res. 30:173732–38 [Google Scholar]
  182. Toffano-Nioche C, Nguyen AN, Kuchly C, Ott A, Gautheret D. 182.  et al. 2012. Transcriptomic profiling of the oyster pathogen Vibrio splendidus opens a window on the evolutionary dynamics of the small RNA repertoire in the Vibrio genus. RNA 18:122201–19 [Google Scholar]
  183. Toledo-Arana A, Dussurget O, Nikitas G, Sesto N, Guet-Revillet H. 183.  et al. 2009. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459:7249950–56 [Google Scholar]
  184. Tomizawa J, Itoh T, Selzer G, Som T. 184.  1981. Inhibition of colE1 RNA primer formation by a plasmid-specified small RNA. PNAS 78:31421–25 [Google Scholar]
  185. Trapnell C, Roberts A, Goff L, Pertea G, Kim D. 185.  et al. 2012. Differential gene and transcript expression analysis of RNA-seq experiments with Tophat and Cufflinks. Nat. Protoc. 7:3562–78 [Google Scholar]
  186. Tree JJ, Granneman S, McAteer SP, Tollervey D, Gally DL. 186.  2014. Identification of bacteriophage-encoded anti-sRNAs in pathogenic Escherichia coli. Mol. Cell 55:2199–213 [Google Scholar]
  187. Tsolis RM, Xavier MN, Santos RL, Bäumler AJ. 187.  2011. How to become a top model: impact of animal experimentation on human Salmonella disease research. Infect. Immun. 79:51806–14 [Google Scholar]
  188. Udekwu KI, Darfeuille F, Vogel J, Reimegård J, Holmqvist E, Wagner EGH. 188.  2005. Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA. Genes Dev. 19:192355–66 [Google Scholar]
  189. Urban JH, Vogel J. 189.  2007. Translational control and target recognition by Escherichia coli small RNAs in vivo. Nucleic Acids Res. 35:31018–37 [Google Scholar]
  190. Ursell LK, Van Treuren W, Metcalf JL, Pirrung M, Gewirtz A, Knight R. 190.  2013. Replenishing our defensive microbes. BioEssays 35:9810–17 [Google Scholar]
  191. Van Opijnen T, Bodi KL, Camilli A. 191.  2009. Tn-seq: high-throughput parallel sequencing for fitness and genetic interaction studies in microorganisms. Nat. Methods 6:10767–72 [Google Scholar]
  192. Van Opijnen T, Camilli A. 192.  2012. A fine scale phenotype-genotype virulence map of a bacterial pathogen. Genome Res. 22:122541–51 [Google Scholar]
  193. Van Opijnen T, Camilli A. 193.  2013. Transposon insertion sequencing: a new tool for systems-level analysis of microorganisms. Nat. Rev. Microbiol. 11:7435–42 [Google Scholar]
  194. Vogel J, Bartels V, Tang TH, Churakov G, Slagter-Jäger JG. 194.  et al. 2003. RNomics in Escherichia coli detects new sRNA species and indicates parallel transcriptional output in bacteria. Nucleic Acids Res. 31:226435–43 [Google Scholar]
  195. Vogel J, Luisi BF. 195.  2011. Hfq and its constellation of RNA. Nat. Rev. Microbiol. 9:8578–89 [Google Scholar]
  196. Vogel J, Sharma CM. 196.  2005. How to find small non-coding RNAs in bacteria. Biol. Chem. 386:121219–38 [Google Scholar]
  197. Voigt K, Sharma CM, Mitschke J, Lambrecht SJ, Voß B. 197.  et al. 2014. Comparative transcriptomics of two environmentally relevant cyanobacteria reveals unexpected transcriptome diversity. ISME J. 8:102056–68 [Google Scholar]
  198. Wade JT, Grainger DC. 198.  2014. Pervasive transcription: illuminating the dark matter of bacterial transcriptomes. Nat. Rev. Microbiol. 12:9647–53 [Google Scholar]
  199. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L. 199.  et al. 2008. Alternative isoform regulation in human tissue transcriptomes. Nature 456:7221470–76 [Google Scholar]
  200. Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S. 200.  2001. Identification of novel small RNAs using comparative genomics and microarrays. Genes Dev. 15:131637–51 [Google Scholar]
  201. Wassarman KM, Storz G. 201.  2000. 6S RNA regulates E. coli RNA polymerase activity. Cell 101:6613–23 [Google Scholar]
  202. Westermann AJ, Gorski SA, Vogel J. 202.  2012. Dual RNA-seq of pathogen and host. Nat. Rev. Microbiol. 10:9618–30 [Google Scholar]
  203. Wright PR, Richter AS, Papenfort K, Mann M, Vogel J. 203.  et al. 2013. Comparative genomics boosts target prediction for bacterial small RNAs. PNAS 110:37E3487–96 [Google Scholar]
  204. Wurtzel O, Sapra R, Chen F, Zhu Y, Simmons BA, Sorek R. 204.  2010. A single-base resolution map of an archaeal transcriptome. Genome Res. 20:1133–41 [Google Scholar]
  205. Zhang A, Altuvia S, Tiwari A, Argaman L, Hengge-Aronis R, Storz G. 205.  1998. The OxyS regulatory RNA represses RpoS translation and binds the Hfq (hf-i) protein. EMBO J. 17:206061–68 [Google Scholar]
  206. Zhang A, Wassarman KM, Rosenow C, Tjaden BC, Storz G, Gottesman S. 206.  2003. Global analysis of small RNA and mRNA targets of Hfq. Mol. Microbiol. 50:41111–24 [Google Scholar]

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