1932

Abstract

Small RNAs (sRNAs) are central regulators of gene expression in bacteria, controlling target genes posttranscriptionally by base pairing with their mRNAs. sRNAs are involved in many cellular processes and have unique regulatory characteristics. In this review, we discuss the properties of regulation by sRNAs and how it differs from and combines with transcriptional regulation. We describe the global characteristics of the sRNA–target networks in bacteria using graph-theoretic approaches and review the local integration of sRNAs in mixed regulatory circuits, including feed-forward loops and their combinations, feedback loops, and circuits made of an sRNA and another regulator, both derived from the same transcript. Finally, we discuss the competition effects in posttranscriptional regulatory networks that may arise over shared targets, shared regulators, and shared resources and how they may lead to signal propagation across the network.

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2017-05-22
2024-06-23
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Literature Cited

  1. Ala U, Karreth FA, Bosia C, Pagnani A, Taulli R. 1.  et al. 2013. Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments. PNAS 110:7154–59 [Google Scholar]
  2. Albert R. 2.  2005. Scale-free networks in cell biology. J. Cell Sci. 118:4947–57 [Google Scholar]
  3. Albert R, Barabasi A-L. 3.  2002. Statistical mechanics of complex networks. Rev. Mod. Phys. 74:47 [Google Scholar]
  4. Alon U. 4.  2007. Network motifs: theory and experimental approaches. Nat. Rev. Genet. 8:450–61 [Google Scholar]
  5. Altuvia S, Zhang A, Argaman L, Tiwari A, Storz G. 5.  1998. The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking ribosome binding. EMBO J 17:6069–75 [Google Scholar]
  6. Arbel-Goren R, Tal A, Friedlander T, Meshner S, Costantino N. 6.  et al. 2013. Effects of post-transcriptional regulation on phenotypic noise in Escherichia coli. . Nucleic Acids Res. 41:4825–34 [Google Scholar]
  7. Arbel-Goren R, Tal A, Parasar B, Dym A, Costantino N. 7.  et al. 2016. Transcript degradation and noise of small RNA-controlled genes in a switch activated network in Escherichia coli. . Nucleic Acids Res. 44:6707–20 [Google Scholar]
  8. Argaman L, Altuvia S. 8.  2000. fhlA repression by OxyS RNA: kissing complex formation at two sites results in a stable antisense-target RNA complex. J. Mol. Biol. 300:1101–12 [Google Scholar]
  9. Barabasi A-L, Oltvai ZN. 9.  2004. Network biology: understanding the cell's functional organization. Nat. Rev. Genet. 5:101–13 [Google Scholar]
  10. Beisel CL, Storz G. 10.  2010. Base pairing small RNAs and their roles in global regulatory networks. FEMS Microbiol. Rev. 34:866–82 [Google Scholar]
  11. Beisel CL, Storz G. 11.  2011. The base-pairing RNA spot 42 participates in a multioutput feedforward loop to help enact catabolite repression in Escherichia coli. . Mol. Cell 41:286–97 [Google Scholar]
  12. Benito Y, Kolb FA, Romby P, Lina G, Etienne J, Vandenesch F. 12.  2000. Probing the structure of RNAIII, the Staphylococcus aureus agr regulatory RNA, and identification of the RNA domain involved in repression of protein A expression. RNA 6:668–79 [Google Scholar]
  13. Bobrovskyy M, Vanderpool CK. 13.  2016. Diverse mechanisms of post-transcriptional repression by the small RNA regulator of glucose-phosphate stress. Mol. Microbiol. 99:254–73 [Google Scholar]
  14. Boisset S, Geissmann T, Huntzinger E, Fechter P, Bendridi N. 14.  et al. 2007. Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism. Genes Dev 21:1353–66 [Google Scholar]
  15. Bosia C, Pagnani A, Zecchina R. 15.  2013. Modelling competing endogenous RNA networks. PLOS ONE 8:e66609 [Google Scholar]
  16. Bossi L, Figueroa-Bossi N. 16.  2016. Competing endogenous RNAs: a target-centric view of small RNA regulation in bacteria. Nature Rev. Microbiol. 14:775–84 [Google Scholar]
  17. Callaway DS, Newman ME, Strogatz SH, Watts DJ. 17.  2000. Network robustness and fragility: percolation on random graphs. Phys. Rev. Lett. 85:5468–71 [Google Scholar]
  18. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O. 18.  et al. 2011. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147:358–69 [Google Scholar]
  19. Chao Y, Papenfort K, Reinhardt R, Sharma CM, Vogel J. 19.  2012. An atlas of Hfq-bound transcripts reveals 3′ UTRs as a genomic reservoir of regulatory small RNAs. EMBO J 31:4005–19 [Google Scholar]
  20. Chao Y, Vogel J. 20.  2016. A 3′ UTR-derived small RNA provides the regulatory noncoding arm of the inner membrane stress response. Mol. Cell 61:352–63 [Google Scholar]
  21. Chen S, Zhang A, Blyn LB, Storz G. 21.  2004. MicC, a second small-RNA regulator of Omp protein expression in Escherichia coli. . J. Bacteriol. 186:6689–97 [Google Scholar]
  22. Coyer J, Andersen J, Forst SA, Inouye M, Delihas N. 22.  1990. micF RNA in ompB mutants of Escherichia coli: different pathways regulate micF RNA levels in response to osmolarity and temperature change. J. Bacteriol. 172:4143–50 [Google Scholar]
  23. De Lay N, Gottesman S. 23.  2012. A complex network of small non-coding RNAs regulate motility in Escherichia coli. . Mol. Microbiol. 86:524–38 [Google Scholar]
  24. Denzler R, Agarwal V, Stefano J, Bartel DP, Stoffel M. 24.  2014. Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. Mol. Cell 54:766–76 [Google Scholar]
  25. Duk MA, Samsonova MG, Samsonov AM. 25.  2014. Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms. BMC Genom 15:Suppl. 12S9 [Google Scholar]
  26. Ebert MS, Sharp PA. 26.  2010. Emerging roles for natural microRNA sponges. Curr. Biol. 20:R858–61 [Google Scholar]
  27. Feng L, Rutherford ST, Papenfort K, Bagert JD, van Kessel JC. 27.  et al. 2015. A Qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics. Cell 160:228–40 [Google Scholar]
  28. Figliuzzi M, Marinari E, De Martino A. 28.  2013. MicroRNAs as a selective channel of communication between competing RNAs: a steady-state theory. Biophys. J. 104:1203–13 [Google Scholar]
  29. Figueroa-Bossi N, Valentini M, Malleret L, Fiorini F, Bossi L. 29.  2009. Caught at its own game: regulatory small RNA inactivated by an inducible transcript mimicking its target. Genes Dev 23:2004–15 [Google Scholar]
  30. Franco-Zorrilla JM, Valli A, Todesco M, Mateos I, Puga MI. 30.  et al. 2007. Target mimicry provides a new mechanism for regulation of microRNA activity. Nat. Genet. 39:1033–37 [Google Scholar]
  31. Gogol EB, Rhodius VA, Papenfort K, Vogel J, Gross CA. 31.  2011. Small RNAs endow a transcriptional activator with essential repressor functions for single-tier control of a global stress regulon. PNAS 108:12875–80 [Google Scholar]
  32. Gottesman S, McCullen CA, Guillier M, Vanderpool CK, Majdalani N. 32.  et al. 2006. Small RNA regulators and the bacterial response to stress. Cold Spring Harb. Symp. Quant. Biol. 71:1–11 [Google Scholar]
  33. Grabowicz M, Koren D, Silhavy TJ. 33.  2016. The CpxQ sRNA negatively regulates Skp to prevent mistargeting of beta-barrel outer membrane proteins into the cytoplasmic membrane. mBio 7:e00312–16 [Google Scholar]
  34. Hall MN, Silhavy TJ. 34.  1981. The ompB locus and the regulation of the major outer membrane porin proteins of Escherichia coli K12. J. Mol. Biol. 146:23–43 [Google Scholar]
  35. Han J-D, Bertin N, Hao T, Goldberg DS, Berriz GF. 35.  et al. 2004. Evidence for dynamically organized modularity in the yeast protein–protein interaction network. Nature 430:88–93 [Google Scholar]
  36. Han K, Tjaden B, Lory S. 36.  2016. GRIL-seq provides a method for identifying direct targets of bacterial small regulatory RNA by in vivo proximity ligation. Nature Microbiol 2:16239 [Google Scholar]
  37. Helwak A, Kudla G, Dudnakova T, Tollervey D. 37.  2013. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153:654–65 [Google Scholar]
  38. Holmqvist E, Unoson C, Reimegard J, Wagner EG. 38.  2012. A mixed double negative feedback loop between the sRNA MicF and the global regulator Lrp. Mol. Microbiol. 84:414–27 [Google Scholar]
  39. Huntzinger E, Boisset S, Saveanu C, Benito Y, Geissmann T. 39.  et al. 2005. Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression. EMBO J. 24:824–35 [Google Scholar]
  40. Hussein R, Lim HN. 40.  2011. Disruption of small RNA signaling caused by competition for Hfq. PNAS 108:1110–15 [Google Scholar]
  41. Hussein R, Lim HN. 41.  2012. Direct comparison of small RNA and transcription factor signaling. Nucleic Acids Res 40:7269–79 [Google Scholar]
  42. Janzon L, Arvidson S. 42.  1990. The role of the delta-lysin gene (hld) in the regulation of virulence genes by the accessory gene regulator (agr) in Staphylococcusaureus. EMBO J. 9:1391–99 [Google Scholar]
  43. Jeong H, Mason SP, Barabasi A-L, Oltvai ZN. 43.  2001. Lethality and centrality in protein networks. Nature 411:41–42 [Google Scholar]
  44. Jost D, Nowojewski A, Levine E. 44.  2013. Regulating the many to benefit the few: role of weak small RNA targets. Biophys J 104:1773–82 [Google Scholar]
  45. Kalyana-Sundaram S, Kumar-Sinha C, Shankar S, Robinson DR, Wu Y-M. 45.  et al. 2012. Expressed pseudogenes in the transcriptional landscape of human cancers. Cell 149:1622–34 [Google Scholar]
  46. Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B. 46.  et al. 2015. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell 161:319–32 [Google Scholar]
  47. Kashtan N, Itzkovitz S, Milo R, Alon U. 47.  2004. Topological generalizations of network motifs. Phys. Rev. E 70:031909 [Google Scholar]
  48. Lahav G. 48.  2008. Oscillations by the p53-Mdm2 feedback loop. Adv. Exp. Med. Biol 64128–38 [Google Scholar]
  49. Lalaouna D, Carrier M-C, Semsey S, Brouard J-S, Wang J. 49.  et al. 2015. A 3′ external transcribed spacer in a tRNA transcript acts as a sponge for small RNAs to prevent transcriptional noise. Mol. Cell 58:393–405 [Google Scholar]
  50. Levine E, Hwa T. 50.  2008. Small RNAs establish gene expression thresholds. Curr. Opin. Microbiol. 11:574–79 [Google Scholar]
  51. Levine E, Zhang Z, Kuhlman T, Hwa T. 51.  2007. Quantitative characteristics of gene regulation by small RNA. PLOS Biol 5:e229 [Google Scholar]
  52. Liu D, Chang X, Liu Z, Chen L, Wang R. 52.  2011. Bistability and oscillations in gene regulation mediated by small noncoding RNAs. PLOS ONE 6:e17029 [Google Scholar]
  53. Majdalani N, Chen S, Murrow J, St John K, Gottesman S. 53.  2001. Regulation of RpoS by a novel small RNA: the characterization of RprA. Mol. Microbiol. 39:1382–94 [Google Scholar]
  54. Mandin P, Gottesman S. 54.  2010. Integrating anaerobic/aerobic sensing and the general stress response through the ArcZ small RNA. EMBO J 29:3094–107 [Google Scholar]
  55. Mandin P, Guillier M. 55.  2013. Expanding control in bacteria: interplay between small RNAs and transcriptional regulators to control gene expression. Curr. Opin. Microbiol. 16:125–32 [Google Scholar]
  56. Mangan S, Alon U. 56.  2003. Structure and function of the feed-forward loop network motif. PNAS 100:11980–85 [Google Scholar]
  57. Massé E, Escorcia FE, Gottesman S. 57.  2003. Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli. . Genes Dev. 17:2374–83 [Google Scholar]
  58. Massé E, Gottesman S. 58.  2002. A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli. . PNAS 99:4620–25 [Google Scholar]
  59. Mehta P, Goyal S, Wingreen NS. 59.  2008. A quantitative comparison of sRNA-based and protein-based gene regulation. Mol. Syst. Biol. 4:221 [Google Scholar]
  60. Melamed S, Peer A, Faigenbaum-Romm R, Gatt YE, Reiss N. 60.  et al. 2016. Global mapping of small RNA-target interactions in bacteria. Mol. Cell 63:884–97 [Google Scholar]
  61. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J. 61.  et al. 2013. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–38 [Google Scholar]
  62. Michaux C, Verneuil N, Hartke A, Giard J-C. 62.  2014. Physiological roles of small RNA molecules. Microbiology 160:1007–19 [Google Scholar]
  63. Mika F, Busse S, Possling A, Berkholz J, Tschowri N. 63.  et al. 2012. Targeting of csgD by the small regulatory RNA RprA links stationary phase, biofilm formation and cell envelope stress in Escherichia coli. . Mol. Microbiol. 84:51–65 [Google Scholar]
  64. Mika F, Hengge R. 64.  2005. A two-component phosphotransfer network involving ArcB, ArcA, and RssB coordinates synthesis and proteolysis of sigmaS (RpoS) in E. coli. . Genes Dev. 19:2770–81 [Google Scholar]
  65. Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U. 65.  2002. Network motifs: simple building blocks of complex networks. Science 298:824–27 [Google Scholar]
  66. Mitarai N, Benjamin J-A, Krishna S, Semsey S, Csiszovszki Z. 66.  et al. 2009. Dynamic features of gene expression control by small regulatory RNAs. PNAS 106:10655–59 [Google Scholar]
  67. Miyakoshi M, Chao Y, Vogel J. 67.  2015. Cross talk between ABC transporter mRNAs via a target mRNA-derived sponge of the GcvB small RNA. EMBO J 34:1478–92 [Google Scholar]
  68. Miyakoshi M, Chao Y, Vogel J. 68.  2015. Regulatory small RNAs from the 3′ regions of bacterial mRNAs. Curr. Opin. Microbiol. 24:132–39 [Google Scholar]
  69. Mizuno T, Chou MY, Inouye M. 69.  1984. A unique mechanism regulating gene expression: Translational inhibition by a complementary RNA transcript (micRNA). PNAS 81:1966–70 [Google Scholar]
  70. Moon K, Gottesman S. 70.  2011. Competition among Hfq-binding small RNAs in Escherichia coli. . Mol. Microbiol. 82:1545–62 [Google Scholar]
  71. Morfeldt E, Taylor D, von Gabain A, Arvidson S. 71.  1995. Activation of alpha-toxin translation in Staphylococcus aureus by the trans-encoded antisense RNA, RNAIII. EMBO J. 14:4569–77 [Google Scholar]
  72. Ng W-L, Bassler BL. 72.  2009. Bacterial quorum-sensing network architectures. Annu. Rev. Genet. 43:197–222 [Google Scholar]
  73. Nitzan M, Fechter P, Peer A, Altuvia Y, Bronesky D. 73.  et al. 2015. A defense-offense multi-layered regulatory switch in a pathogenic bacterium. Nucleic Acids Res 43:1357–69 [Google Scholar]
  74. Nitzan M, Shimoni Y, Rosolio O, Margalit H, Biham O. 74.  2015. Stochastic analysis of bistability in coherent mixed feedback loops combining transcriptional and posttranscriptional regulations. Phys. Rev. E 91:052706 [Google Scholar]
  75. Nitzan M, Steiman-Shimony A, Altuvia Y, Biham O, Margalit H. 75.  2014. Interactions between distant ceRNAs in regulatory networks. Biophys. J. 106:2254–66 [Google Scholar]
  76. Novick R. 76.  2000. Pathogenicity factors and their regulation. Gram-Positive Pathogens VA Fischetti, RP Novick, JJ Ferretti, DA Portnov, JJ Rood 392–407 Washington, DC: ASM Press [Google Scholar]
  77. Overgaard M, Johansen J, Møller-Jensen J, Valentin-Hansen P. 77.  2009. Switching off small RNA regulation with trap-mRNA. Mol. Microbiol. 73:790–800 [Google Scholar]
  78. Papenfort K, Espinosa E, Casadesus J, Vogel J. 78.  2015. Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal DNA transfer in Salmonella. PNAS 112:E4772–81 [Google Scholar]
  79. Papenfort K, Vanderpool CK. 79.  2015. Target activation by regulatory RNAs in bacteria. FEMS Microbiol. Rev. 39:362–78 [Google Scholar]
  80. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. 80.  2010. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465:1033–38 [Google Scholar]
  81. Prévost K, Desnoyers G, Jacques J-F, Lavoie F, Massé E. 81.  2011. Small RNA-induced mRNA degradation achieved through both translation block and activated cleavage. Genes Dev 25:385–96 [Google Scholar]
  82. Ramirez-Peña E, Treviño J, Liu Z, Perez N, Sumby P. 82.  2010. The group A Streptococcus small regulatory RNA FasX enhances streptokinase activity by increasing the stability of the ska mRNA transcript. Mol. Microbiol. 78:1332–47 [Google Scholar]
  83. Sedlyarova N, Shamovsky I, Bharati BK, Epshtein V, Chen J. 83.  et al. 2016. sRNA-mediated control of transcription termination in E. . coli. Cell 167:111–21 [Google Scholar]
  84. Shen-Orr SS, Milo R, Mangan S, Alon U. 84.  2002. Network motifs in the transcriptional regulation network of Escherichia coli. Nat. Genet. 31:64–68 [Google Scholar]
  85. Shimoni Y, Friedlander G, Hetzroni G, Niv G, Altuvia S. 85.  et al. 2007. Regulation of gene expression by small non-coding RNAs: a quantitative view. Mol. Syst. Biol. 3:138 [Google Scholar]
  86. Storz G, Vogel J, Wassarman KM. 86.  2011. Regulation by small RNAs in bacteria: expanding frontiers. Mol. Cell 43:880–91 [Google Scholar]
  87. Sumazin P, Yang X, Chiu H-S, Chung W-J, Iyer A. 87.  et al. 2011. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell 147:370–81 [Google Scholar]
  88. Thomason MK, Fontaine F, De Lay N, Storz G. 88.  2012. A small RNA that regulates motility and biofilm formation in response to changes in nutrient availability in Escherichia coli. . Mol. Microbiol. 84:17–35 [Google Scholar]
  89. Thomson DW, Dinger ME. 89.  2016. Endogenous microRNA sponges: evidence and controversy. Nat. Rev. Genet. 17:272–83 [Google Scholar]
  90. Tree JJ, Granneman S, McAteer SP, Tollervey D, Gally DL. 90.  2014. Identification of bacteriophage-encoded anti-sRNAs in pathogenic Escherichia coli. . Mol. Cell 55:199–213 [Google Scholar]
  91. Vanderpool CK, Balasubramanian D, Lloyd CR. 91.  2011. Dual-function RNA regulators in bacteria. Biochimie 93:1943–49 [Google Scholar]
  92. Večerek B, Moll I, Bläsi U. 92.  2007. Control of Fur synthesis by the non-coding RNA RyhB and iron-responsive decoding. EMBO J 26:965–75 [Google Scholar]
  93. Vogel J, Luisi BF. 93.  2011. Hfq and its constellation of RNA. Nat. Rev. Microbiol. 9:578–89 [Google Scholar]
  94. Wadler CS, Vanderpool CK. 94.  2007. A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide. PNAS 104:20454–59 [Google Scholar]
  95. Wagner EG, Romby P. 95.  2015. Small RNAs in bacteria and archaea: who they are, what they do, and how they do it. Adv. Genet. 90:133–208 [Google Scholar]
  96. Wang D, Yan K-K, Sisu C, Cheng C, Rozowsky J. 96.  et al. 2015. Loregic: a method to characterize the cooperative logic of regulatory factors. PLOS Comput. Biol. 11:e1004132 [Google Scholar]
  97. Waters LS, Storz G. 97.  2009. Regulatory RNAs in bacteria. Cell 136:615–28 [Google Scholar]
  98. Waters SA, McAteer SP, Kudla G, Pang I, Deshpande NP. 98.  et al. 2017. Small RNA interactome of pathogenic E. coli revealed through crosslinking of RNase E. EMBO J. 36:374–87 [Google Scholar]
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