1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Small Regulatory RNAs in the Enterobacterial Response to Envelope Damage and Oxidative Stress

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy this Microbiology Spectrum Article
Price Non-Member $15.00
  • Authors: Kathrin S. Fröhlich1, Susan Gottesman2
  • Editors: Gisela Storz3, Kai Papenfort4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Biology I, Microbiology, LMU Munich, 82152 Martinsried, Germany; 2: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892; 3: Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; 4: Department of Biology I, Microbiology, LMU Munich, Martinsried, Germany
  • Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0022-2018
  • Received 24 January 2018 Accepted 05 March 2018 Published 06 July 2018
  • Kathrin S. Fröhlich, [email protected]; Susan Gottesman, [email protected]
image of Small Regulatory RNAs in the Enterobacterial Response to Envelope Damage and Oxidative Stress
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Small Regulatory RNAs in the Enterobacterial Response to Envelope Damage and Oxidative Stress, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/6/4/RWR-0022-2018-1.gif /docserver/preview/fulltext/microbiolspec/6/4/RWR-0022-2018-2.gif
  • Abstract:

    The ability of bacteria to thrive in diverse habitats and to adapt to ever-changing environmental conditions relies on the rapid and stringent modulation of gene expression. It has become evident in the past decade that small regulatory RNAs (sRNAs) are central components of networks controlling the bacterial responses to stress. Functioning at the posttranscriptional level, sRNAs base-pair with cognate mRNAs to alter translation, stability, or both to either repress or activate the targeted transcripts; the RNA chaperone Hfq participates in stabilizing sRNAs and in promoting pairing between target and sRNA. In particular, sRNAs act at the heart of crucial stress responses, including those dedicated to overcoming membrane damage and oxidative stress, discussed here. The bacterial cell envelope is the outermost protective barrier against the environment and thus is constantly monitored and remodeled. Here, we review the integration of sRNAs into the complex networks of several major envelope stress responses of Gram-negative bacteria, including the RpoE (σ), Cpx, and Rcs regulons. Oxidative stress, caused by bacterial respiratory activity or induced by toxic molecules, can lead to significant damage of cellular components. In and related bacteria, sRNAs also contribute significantly to the function of the RpoS (σ)-dependent general stress response as well as the specific OxyR- and SoxR/S-mediated responses to oxidative damage. Their activities in gene regulation and crosstalk to other stress-induced regulons are highlighted.

  • Citation: Fröhlich K, Gottesman S. 2018. Small Regulatory RNAs in the Enterobacterial Response to Envelope Damage and Oxidative Stress. Microbiol Spectrum 6(4):RWR-0022-2018. doi:10.1128/microbiolspec.RWR-0022-2018.

References

1. Papenfort K, Vanderpool CK. 2015. Target activation by regulatory RNAs in bacteria. FEMS Microbiol Rev 39:362–378. [PubMed]
2. Waters LS, Storz G. 2009. Regulatory RNAs in bacteria. Cell 136:615–628. [PubMed]
3. Storz G, Vogel J, Wassarman KM. 2011. Regulation by small RNAs in bacteria: expanding frontiers. Mol Cell 43:880–891. [PubMed]
4. Zhang A, Schu DJ, Tjaden BC, Storz G, Gottesman S. 2013. Mutations in interaction surfaces differentially impact E. coli Hfq association with small RNAs and their mRNA targets. J Mol Biol 425:3678–3697. [PubMed]
5. Kawamoto H, Koide Y, Morita T, Aiba H. 2006. Base-pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq. Mol Microbiol 61:1013–1022. [PubMed]
6. Melamed S, Peer A, Faigenbaum-Romm R, Gatt YE, Reiss N, Bar A, Altuvia Y, Argaman L, Margalit H. 2016. Global mapping of small RNA-target interactions in bacteria. Mol Cell 63:884–897. [PubMed]
7. Soper TJ, Woodson SA. 2008. The rpoS mRNA leader recruits Hfq to facilitate annealing with DsrA sRNA. RNA 14:1907–1917. [PubMed]
8. Tsui HC, Leung HC, Winkler ME. 1994. Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12. Mol Microbiol 13:35–49. [PubMed]
9. Battesti A, Majdalani N, Gottesman S. 2011. The RpoS-mediated general stress response in Escherichia coli. Annu Rev Microbiol 65:189–213. [PubMed]
10. Weber H, Polen T, Heuveling J, Wendisch VF, Hengge R. 2005. Genome-wide analysis of the general stress response network in Escherichia coli: σS-dependent genes, promoters, and sigma factor selectivity. J Bacteriol 187:1591–1603. [PubMed]
11. Dong T, Schellhorn HE. 2009. Control of RpoS in global gene expression of Escherichia coli in minimal media. Mol Genet Genomics 281:19–33. [PubMed]
12. Patten CL, Kirchhof MG, Schertzberg MR, Morton RA, Schellhorn HE. 2004. Microarray analysis of RpoS-mediated gene expression in Escherichia coli K-12. Mol Genet Genomics 272:580–591. [PubMed]
13. Muffler A, Fischer D, Hengge-Aronis R. 1996. The RNA-binding protein HF-I, known as a host factor for phage Qβ RNA replication, is essential for rpoS translation in Escherichia coli. Genes Dev 10:1143–1151. [PubMed]
14. Muffler A, Traulsen DD, Fischer D, Lange R, Hengge-Aronis R. 1997. The RNA-binding protein HF-I plays a global regulatory role which is largely, but not exclusively, due to its role in expression of the σS subunit of RNA polymerase in Escherichia coli. J Bacteriol 179:297–300. [PubMed]
15. Opdyke JA, Fozo EM, Hemm MR, Storz G. 2011. RNase III participates in GadY-dependent cleavage of the gadX-gadW mRNA. J Mol Biol 406:29–43. [PubMed]
16. Opdyke JA, Kang JG, Storz G. 2004. GadY, a small-RNA regulator of acid response genes in Escherichia coli. J Bacteriol 186:6698–6705. [PubMed]
17. Hao Y, Updegrove TB, Livingston NN, Storz G. 2016. Protection against deleterious nitrogen compounds: role of σS-dependent small RNAs encoded adjacent to sdiA. Nucleic Acids Res 44:6935–6948. [PubMed]
18. Silva IJ, Ortega AD, Viegas SC, García-Del Portillo F, Arraiano CM. 2013. An RpoS-dependent sRNA regulates the expression of a chaperone involved in protein folding. RNA 19:1253–1265. [PubMed]
19. Parker A, Gottesman S. 2016. Small RNA regulation of TolC, the outer membrane component of bacterial multidrug transporters. J Bacteriol 198:1101–1113. [PubMed]
20. Fröhlich KS, Haneke K, Papenfort K, Vogel J. 2016. The target spectrum of SdsR small RNA in Salmonella. Nucleic Acids Res 44:10406–10422. [PubMed]
21. Fröhlich KS, Papenfort K, Berger AA, Vogel J. 2012. A conserved RpoS-dependent small RNA controls the synthesis of major porin OmpD. Nucleic Acids Res 40:3623–3640. [PubMed]
22. Gutierrez A, Laureti L, Crussard S, Abida H, Rodríguez-Rojas A, Blázquez J, Baharoglu Z, Mazel D, Darfeuille F, Vogel J, Matic I. 2013. β-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity. Nat Commun 4:1610. doi:10.1038/ncomms2607. [PubMed]
23. Guisbert E, Rhodius VA, Ahuja N, Witkin E, Gross CA. 2007. Hfq modulates the σE-mediated envelope stress response and the σ32-mediated cytoplasmic stress response in Escherichia coli. J Bacteriol 189:1963–1973. [PubMed]
24. Figueroa-Bossi N, Lemire S, Maloriol D, Balbontín R, Casadesús J, Bossi L. 2006. Loss of Hfq activates the σE-dependent envelope stress response in Salmonella enterica. Mol Microbiol 62:838–852. [PubMed]
25. Vogel J, Papenfort K. 2006. Small non-coding RNAs and the bacterial outer membrane. Curr Opin Microbiol 9:605–611. [PubMed]
26. Gogol EB, Rhodius VA, Papenfort K, Vogel J, Gross CA. 2011. Small RNAs endow a transcriptional activator with essential repressor functions for single-tier control of a global stress regulon. Proc Natl Acad Sci U S A 108:12875–12880. [PubMed]
27. Massé E, Gottesman S. 2002. A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli. Proc Natl Acad Sci U S A 99:4620–4625. [PubMed]
28. Schu DJ, Zhang A, Gottesman S, Storz G. 2015. Alternative Hfq-sRNA interaction modes dictate alternative mRNA recognition. EMBO J 34:2557–2573. [PubMed]
29. Mutalik VK, Nonaka G, Ades SE, Rhodius VA, Gross CA. 2009. Promoter strength properties of the complete σE regulon of Escherichia coli and Salmonella enterica. J Bacteriol 191:7279–7287. [PubMed]
30. Beisel CL, Storz G. 2011. The base-pairing RNA Spot 42 participates in a multioutput feedforward loop to help enact catabolite repression in Escherichia coli. Mol Cell 41:286–297. [PubMed]
31. Massé E, Salvail H, Desnoyers G, Arguin M. 2007. Small RNAs controlling iron metabolism. Curr Opin Microbiol 10:140–145. [PubMed]
32. Altuvia S, Weinstein-Fischer D, Zhang A, Postow L, Storz G. 1997. A small, stable RNA induced by oxidative stress: role as a pleiotropic regulator and antimutator. Cell 90:43–53. [PubMed]
33. Coornaert A, Lu A, Mandin P, Springer M, Gottesman S, Guillier M. 2010. MicA sRNA links the PhoP regulon to cell envelope stress. Mol Microbiol 76:467–479. [PubMed]
34. Nikaido H. 2003. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593–656. [PubMed]
35. Silhavy TJ, Kahne D, Walker S. 2010. The bacterial cell envelope. Cold Spring Harb Perspect Biol 2:a000414. doi:10.1101/cshperspect.a000414. [PubMed]
36. Vollmer W, Blanot D, de Pedro MA. 2008. Peptidoglycan structure and architecture. FEMS Microbiol Rev 32:149–167. [PubMed]
37. Braun V. 1975. Covalent lipoprotein from the outer membrane of Escherichia coli. Biochim Biophys Acta 415:335–377. [PubMed]
38. Li GW, Burkhardt D, Gross C, Weissman JS. 2014. Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Cell 157:624–635. [PubMed]
39. Inouye M, Shaw J, Shen C. 1972. The assembly of a structural lipoprotein in the envelope of Escherichia coli. J Biol Chem 247:8154–8159. [PubMed]
40. Whitfield C, Trent MS. 2014. Biosynthesis and export of bacterial lipopolysaccharides. Annu Rev Biochem 83:99–128. [PubMed]
41. Maldonado RF, Sá-Correia I, Valvano MA. 2016. Lipopolysaccharide modification in Gram-negative bacteria during chronic infection. FEMS Microbiol Rev 40:480–493. [PubMed]
42. Braun V, Endriss F. 2007. Energy-coupled outer membrane transport proteins and regulatory proteins. Biometals 20:219–231. [PubMed]
43. Grabowicz M, Silhavy TJ. 2017. Envelope stress responses: an interconnected safety net. Trends Biochem Sci 42:232–242. [PubMed]
44. Bury-Moné S, Nomane Y, Reymond N, Barbet R, Jacquet E, Imbeaud S, Jacq A, Bouloc P. 2009. Global analysis of extracytoplasmic stress signaling in Escherichia coli. PLoS Genet 5:e1000651. doi:10.1371/journal.pgen.1000651. [PubMed]
45. Raina S, Missiakas D, Georgopoulos C. 1995. The rpoE gene encoding the σE24) heat shock sigma factor of Escherichia coli. EMBO J 14:1043–1055. [PubMed]
46. Ades SE, Grigorova IL, Gross CA. 2003. Regulation of the alternative sigma factor σE during initiation, adaptation, and shutoff of the extracytoplasmic heat shock response in Escherichia coli. J Bacteriol 185:2512–2519. [PubMed]
47. Ades SE. 2004. Control of the alternative sigma factor σE in Escherichia coli. Curr Opin Microbiol 7:157–162. [PubMed]
48. Walsh NP, Alba BM, Bose B, Gross CA, Sauer RT. 2003. OMP peptide signals initiate the envelope-stress response by activating DegS protease via relief of inhibition mediated by its PDZ domain. Cell 113:61–71. [PubMed]
49. Lima S, Guo MS, Chaba R, Gross CA, Sauer RT. 2013. Dual molecular signals mediate the bacterial response to outer-membrane stress. Science 340:837–841. [PubMed]
50. Skovierova H, Rowley G, Rezuchova B, Homerova D, Lewis C, Roberts M, Kormanec J. 2006. Identification of the σE regulon of Salmonella enterica serovar Typhimurium. Microbiology 152:1347–1359. [PubMed]
51. Rhodius VA, Suh WC, Nonaka G, West J, Gross CA. 2006. Conserved and variable functions of the σE stress response in related genomes. PLoS Biol 4:e2. doi:10.1371/journal.pbio.0040002. [PubMed]
52. Chao Y, Papenfort K, Reinhardt R, Sharma CM, Vogel J. 2012. An atlas of Hfq-bound transcripts reveals 3′ UTRs as a genomic reservoir of regulatory small RNAs. EMBO J 31:4005–4019. [PubMed]
53. Zhang A, Wassarman KM, Rosenow C, Tjaden BC, Storz G, Gottesman S. 2003. Global analysis of small RNA and mRNA targets of Hfq. Mol Microbiol 50:1111–1124. [PubMed]
54. Hayden JD, Ades SE. 2008. The extracytoplasmic stress factor, σE, is required to maintain cell envelope integrity in Escherichia coli. PLoS One 3:e1573. doi:10.1371/journal.pone.0001573. [PubMed]
55. De Las Peñas A, Connolly L, Gross CA. 1997. σE is an essential sigma factor in Escherichia coli. J Bacteriol 179:6862–6864.
56. Papenfort K, Bouvier M, Mika F, Sharma CM, Vogel J. 2010. Evidence for an autonomous 5′ target recognition domain in an Hfq-associated small RNA. Proc Natl Acad Sci U S A 107:20435–20440. [PubMed]
57. Bouvier M, Sharma CM, Mika F, Nierhaus KH, Vogel J. 2008. Small RNA binding to 5′ mRNA coding region inhibits translational initiation. Mol Cell 32:827–837. [PubMed]
58. Celesnik H, Deana A, Belasco JG. 2007. Initiation of RNA decay in Escherichia coli by 5′ pyrophosphate removal. Mol Cell 27:79–90. [PubMed]
59. Emory SA, Bouvet P, Belasco JG. 1992. A 5′-terminal stem-loop structure can stabilize mRNA in Escherichia coli. Genes Dev 6:135–148. [PubMed]
60. Papenfort K, Pfeiffer V, Mika F, Lucchini S, Hinton JC, Vogel J. 2006. σE-Dependent small RNAs of Salmonella respond to membrane stress by accelerating global omp mRNA decay. Mol Microbiol 62:1674–1688. [PubMed]
61. Song T, Mika F, Lindmark B, Liu Z, Schild S, Bishop A, Zhu J, Camilli A, Johansson J, Vogel J, Wai SN. 2008. A new Vibrio cholerae sRNA modulates colonization and affects release of outer membrane vesicles. Mol Microbiol 70:100–111. [PubMed]
62. Song T, Sabharwal D, Wai SN. 2010. VrrA mediates Hfq-dependent regulation of OmpT synthesis in Vibrio cholerae. J Mol Biol 400:682–688. [PubMed]
63. Song T, Sabharwal D, Gurung JM, Cheng AT, Sjöström AE, Yildiz FH, Uhlin BE, Wai SN. 2014. Vibrio cholerae utilizes direct sRNA regulation in expression of a biofilm matrix protein. PLoS One 9:e101280. doi:10.1371/journal.pone.0101280. [PubMed]
64. Sabharwal D, Song T, Papenfort K, Wai SN. 2015. The VrrA sRNA controls a stationary phase survival factor Vrp of Vibrio cholerae. RNA Biol 12:186–196. [PubMed]
65. Klein G, Kobylak N, Lindner B, Stupak A, Raina S. 2014. Assembly of lipopolysaccharide in Escherichia coli requires the essential LapB heat shock protein. J Biol Chem 289:14829–14853. [PubMed]
66. Guo MS, Updegrove TB, Gogol EB, Shabalina SA, Gross CA, Storz G. 2014. MicL, a new σE-dependent sRNA, combats envelope stress by repressing synthesis of Lpp, the major outer membrane lipoprotein. Genes Dev 28:1620–1634. [PubMed]
67. Raivio TL. 2014. Everything old is new again: an update on current research on the Cpx envelope stress response. Biochim Biophys Acta 1843:1529–1541. [PubMed]
68. Mileykovskaya E, Dowhan W. 1997. The Cpx two-component signal transduction pathway is activated in Escherichia coli mutant strains lacking phosphatidylethanolamine. J Bacteriol 179:1029–1034. [PubMed]
69. Raivio TL, Silhavy TJ. 1997. Transduction of envelope stress in Escherichia coli by the Cpx two-component system. J Bacteriol 179:7724–7733.
70. Snyder WB, Davis LJ, Danese PN, Cosma CL, Silhavy TJ. 1995. Overproduction of NlpE, a new outer membrane lipoprotein, suppresses the toxicity of periplasmic LacZ by activation of the Cpx signal transduction pathway. J Bacteriol 177:4216–4223. [PubMed]
71. Delhaye A, Collet JF, Laloux G. 2016. Fine-tuning of the Cpx envelope stress response is required for cell wall homeostasis in Escherichia coli. mBio 7:e00047-e16. doi:10.1128/mBio.00047-16. [PubMed]
72. Vogt SL, Nevesinjac AZ, Humphries RM, Donnenberg MS, Armstrong GD, Raivio TL. 2010. The Cpx envelope stress response both facilitates and inhibits elaboration of the enteropathogenic Escherichia coli bundle-forming pilus. Mol Microbiol 76:1095–1110. [PubMed]
73. Guest RL, Wang J, Wong JL, Raivio TL. 2017. A bacterial stress response regulates respiratory protein complexes to control envelope stress adaptation. J Bacteriol 199:e00153-17. doi:10.1128/JB.00153-17. [PubMed]
74. Danese PN, Silhavy TJ. 1998. CpxP, a stress-combative member of the Cpx regulon. J Bacteriol 180:831–839. [PubMed]
75. Raivio TL, Popkin DL, Silhavy TJ. 1999. The Cpx envelope stress response is controlled by amplification and feedback inhibition. J Bacteriol 181:5263–5272. [PubMed]
76. Chao Y, Vogel J. 2016. A 3′ UTR-derived small RNA provides the regulatory noncoding arm of the inner membrane stress response. Mol Cell 61:352–363. [PubMed]
77. Grabowicz M, Koren D, Silhavy TJ. 2016. The CpxQ sRNA negatively regulates Skp to prevent mistargeting of β-barrel outer membrane proteins into the cytoplasmic membrane. mBio 7:e00312-16. doi:10.1128/mBio.00312-16. [PubMed]
78. Vogt SL, Evans AD, Guest RL, Raivio TL. 2014. The Cpx envelope stress response regulates and is regulated by small noncoding RNAs. J Bacteriol 196:4229–4238. [PubMed]
79. Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S. 2001. Identification of novel small RNAs using comparative genomics and microarrays. Genes Dev 15:1637–1651. [PubMed]
80. De Lay N, Gottesman S. 2009. The Crp-activated small noncoding regulatory RNA CyaR (RyeE) links nutritional status to group behavior. J Bacteriol 191:461–476. [PubMed]
81. Johansen J, Eriksen M, Kallipolitis B, Valentin-Hansen P. 2008. Down-regulation of outer membrane proteins by noncoding RNAs: unraveling the cAMP-CRP- and σE-dependent CyaR-ompX regulatory case. J Mol Biol 383:1–9. [PubMed]
82. Papenfort K, Pfeiffer V, Lucchini S, Sonawane A, Hinton JC, Vogel J. 2008. Systematic deletion of Salmonella small RNA genes identifies CyaR, a conserved CRP-dependent riboregulator of OmpX synthesis. Mol Microbiol 68:890–906. [PubMed]
83. Majdalani N, Gottesman S. 2005. The Rcs phosphorelay: a complex signal transduction system. Annu Rev Microbiol 59:379–405. [PubMed]
84. Laubacher ME, Ades SE. 2008. The Rcs phosphorelay is a cell envelope stress response activated by peptidoglycan stress and contributes to intrinsic antibiotic resistance. J Bacteriol 190:2065–2074. [PubMed]
85. Majdalani N, Chen S, Murrow J, St John K, Gottesman S. 2001. Regulation of RpoS by a novel small RNA: the characterization of RprA. Mol Microbiol 39:1382–1394. [PubMed]
86. Papenfort K, Espinosa E, Casadesús J, Vogel J. 2015. Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal DNA transfer in Salmonella. Proc Natl Acad Sci U S A 112:E4772–E4781. [PubMed]
87. Madhugiri R, Basineni SR, Klug G. 2010. Turn-over of the small non-coding RNA RprA in E. coli is influenced by osmolarity. Mol Genet Genomics 284:307–318. [PubMed]
88. Holmqvist E, Reimegård J, Sterk M, Grantcharova N, Römling U, Wagner EG. 2010. Two antisense RNAs target the transcriptional regulator CsgD to inhibit curli synthesis. EMBO J 29:1840–1850. [PubMed]
89. Thomason MK, Fontaine F, De Lay N, Storz G. 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. [PubMed]
90. Mika F, Busse S, Possling A, Berkholz J, Tschowri N, Sommerfeldt N, Pruteanu M, Hengge R. 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. [PubMed]
91. Jørgensen MG, Nielsen JS, Boysen A, Franch T, Møller-Jensen J, Valentin-Hansen P. 2012. Small regulatory RNAs control the multi-cellular adhesive lifestyle of Escherichia coli. Mol Microbiol 84:36–50. [PubMed]
92. Ogasawara H, Yamamoto K, Ishihama A. 2011. Role of the biofilm master regulator CsgD in cross-regulation between biofilm formation and flagellar synthesis. J Bacteriol 193:2587–2597. [PubMed]
93. Boehm A, Vogel J. 2012. The csgD mRNA as a hub for signal integration via multiple small RNAs. Mol Microbiol 84:1–5. [PubMed]
94. Pogliano J, Lynch AS, Belin D, Lin EC, Beckwith J. 1997. Regulation of Escherichia coli cell envelope proteins involved in protein folding and degradation by the Cpx two-component system. Genes Dev 11:1169–1182. [PubMed]
95. Pratt LA, Hsing W, Gibson KE, Silhavy TJ. 1996. From acids to osmZ: multiple factors influence synthesis of the OmpF and OmpC porins in Escherichia coli. Mol Microbiol 20:911–917. [PubMed]
96. Alphen WV, Lugtenberg B. 1977. Influence of osmolarity of the growth medium on the outer membrane protein pattern of Escherichia coli. J Bacteriol 131:623–630. [PubMed]
97. Chen S, Zhang A, Blyn LB, Storz G. 2004. MicC, a second small-RNA regulator of Omp protein expression in Escherichia coli. J Bacteriol 186:6689–6697. [PubMed]
98. Mizuno T, Chou MY, Inouye M. 1984. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc Natl Acad Sci U S A 81:1966–1970. [PubMed]
99. Guillier M, Gottesman S. 2006. Remodelling of the Escherichia coli outer membrane by two small regulatory RNAs. Mol Microbiol 59:231–247. [PubMed]
100. Brosse A, Korobeinikova A, Gottesman S, Guillier M. 2016. Unexpected properties of sRNA promoters allow feedback control via regulation of a two-component system. Nucleic Acids Res 44:9650–9666.
101. Singh SP, Williams YU, Klebba PE, Macchia P, Miller S. 2000. Immune recognition of porin and lipopolysaccharide epitopes of Salmonella typhimurium in mice. Microb Pathog 28:157–167. [PubMed]
102. Needham BD, Trent MS. 2013. Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis. Nat Rev Microbiol 11:467–481. [PubMed]
103. Corcoran CP, Podkaminski D, Papenfort K, Urban JH, Hinton JC, Vogel J. 2012. Superfolder GFP reporters validate diverse new mRNA targets of the classic porin regulator, MicF RNA. Mol Microbiol 84:428–445. [PubMed]
104. Groisman EA. 2001. The pleiotropic two-component regulatory system PhoP-PhoQ. J Bacteriol 183:1835–1842. [PubMed]
105. Miller SI, Kukral AM, Mekalanos JJ. 1989. A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci U S A 86:5054–5058. [PubMed]
106. Sittka A, Lucchini S, Papenfort K, Sharma CM, Rolle K, Binnewies TT, Hinton JC, Vogel J. 2008. Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator, Hfq. PLoS Genet 4:e1000163. doi:10.1371/journal.pgen.1000163. [PubMed]
107. Acuña LG, Barros MJ, Peñaloza D, Rodas PI, Paredes-Sabja D, Fuentes JA, Gil F, Calderón IL. 2016. A feed-forward loop between SroC and MgrR small RNAs modulates the expression of eptB and the susceptibility to polymyxin B in Salmonella Typhimurium. Microbiology 162:1996–2004. [PubMed]
108. Miyakoshi M, Chao Y, Vogel J. 2015. Cross talk between ABC transporter mRNAs via a target mRNA-derived sponge of the GcvB small RNA. EMBO J 34:1478–1492. [PubMed]
109. Moon K, Gottesman S. 2009. A PhoQ/P-regulated small RNA regulates sensitivity of Escherichia coli to antimicrobial peptides. Mol Microbiol 74:1314–1330. [PubMed]
110. Reynolds CM, Kalb SR, Cotter RJ, Raetz CR. 2005. A phosphoethanolamine transferase specific for the outer 3-deoxy-d-manno-octulosonic acid residue of Escherichia coli lipopolysaccharide. Identification of the eptB gene and Ca2+ hypersensitivity of an eptB deletion mutant. J Biol Chem 280:21202–21211. [PubMed]
111. Moon K, Six DA, Lee HJ, Raetz CR, Gottesman S. 2013. Complex transcriptional and post-transcriptional regulation of an enzyme for lipopolysaccharide modification. Mol Microbiol 89:52–64. [PubMed]
112. Mandin P, Gottesman S. 2010. Integrating anaerobic/aerobic sensing and the general stress response through the ArcZ small RNA. EMBO J 29:3094–3107. [PubMed]
113. Coornaert A, Chiaruttini C, Springer M, Guillier M. 2013. Post-transcriptional control of the Escherichia coli PhoQ-PhoP two-component system by multiple sRNAs involves a novel pairing region of GcvB. PLoS Genet 9:e1003156. doi:10.1371/journal.pgen.1003156. [PubMed]
114. Chen J, Gottesman S. 2017. Hfq links translation repression to stress-induced mutagenesis in E. coli. Genes Dev 31:1382–1395. [PubMed]
115. Sharma CM, Papenfort K, Pernitzsch SR, Mollenkopf HJ, Hinton JC, Vogel J. 2011. Pervasive post-transcriptional control of genes involved in amino acid metabolism by the Hfq-dependent GcvB small RNA. Mol Microbiol 81:1144–1165. [PubMed]
116. Storz G, Imlay JA. 1999. Oxidative stress. Curr Opin Microbiol 2:188–194.
117. Imlay JA. 2013. The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat Rev Microbiol 11:443–454. [PubMed]
118. Frawley ER, Fang FC. 2014. The ins and outs of bacterial iron metabolism. Mol Microbiol 93:609–616. [PubMed]
119. Alekshun MN, Levy SB. 1997. Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob Agents Chemother 41:2067–2075. [PubMed]
120. Demple B. 1996. Redox signaling and gene control in the Escherichia coli soxRS oxidative stress regulon—a review. Gene 179:53–57.
121. Rosner JL, Dangi B, Gronenborn AM, Martin RG. 2002. Posttranscriptional activation of the transcriptional activator Rob by dipyridyl in Escherichia coli. J Bacteriol 184:1407–1416. [PubMed]
122. Nunoshiba T, deRojas-Walker T, Wishnok JS, Tannenbaum SR, Demple B. 1993. Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages. Proc Natl Acad Sci U S A 90:9993–9997. [PubMed]
123. Lee HJ, Gottesman S. 2016. sRNA roles in regulating transcriptional regulators: Lrp and SoxS regulation by sRNAs. Nucleic Acids Res 44:6907–6923. [PubMed]
124. Zhang A, Altuvia S, Tiwari A, Argaman L, Hengge-Aronis R, Storz G. 1998. The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF-I) protein. EMBO J 17:6061–6068. [PubMed]
125. Schellhorn HE, Hassan HM. 1988. Transcriptional regulation of katE in Escherichia coli K-12. J Bacteriol 170:4286–4292.
126. Becker-Hapak M, Eisenstark A. 1995. Role of rpoS in the regulation of glutathione oxidoreductase (gor) in Escherichia coli. FEMS Microbiol Lett 134:39–44.
127. Moon K, Gottesman S. 2011. Competition among Hfq-binding small RNAs in Escherichia coli. Mol Microbiol 82:1545–1562. [PubMed]
128. Hämmerle H, Večerek B, Resch A, Bläsi U. 2013. Duplex formation between the sRNA DsrA and rpoS mRNA is not sufficient for efficient RpoS synthesis at low temperature. RNA Biol 10:1834–1841. [PubMed]
129. González-Flecha B, Demple B. 1999. Role for the oxyS gene in regulation of intracellular hydrogen peroxide in Escherichia coli. J Bacteriol 181:3833–3836. [PubMed]
130. Argaman L, Altuvia S. 2000. fhlA repression by OxyS RNA: kissing complex formation at two sites results in a stable antisense-target RNA complex. J Mol Biol 300:1101–1112. [PubMed]
131. Schlensog V, Böck A. 1990. Identification and sequence analysis of the gene encoding the transcriptional activator of the formate hydrogenlyase system of Escherichia coli. Mol Microbiol 4:1319–1327. [PubMed]
132. Altuvia S, Zhang A, Argaman L, Tiwari A, Storz G. 1998. The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking ribosome binding. EMBO J 17:6069–6075. [PubMed]
133. Tjaden B, Goodwin SS, Opdyke JA, Guillier M, Fu DX, Gottesman S, Storz G. 2006. Target prediction for small, noncoding RNAs in bacteria. Nucleic Acids Res 34:2791–2802. [PubMed]
134. Barshishat S, Elgrably-Weiss M, Edelstein J, Georg J, Govindarajan S, Haviv M, Wright PR, Hess WR, Altuvia S. 2017. OxyS small RNA induces cell cycle arrest to allow DNA damage repair. EMBO J 37:413–426. [PubMed]
135. Ray-Soni A, Bellecourt MJ, Landick R. 2016. Mechanisms of bacterial transcription termination: all good things must end. Annu Rev Biochem 85:319–347. [PubMed]
136. Conter A, Bouché JP, Dassain M. 1996. Identification of a new inhibitor of essential division gene ftsZ as the kil gene of defective prophage Rac. J Bacteriol 178:5100–5104. [PubMed]
137. Li GM. 2008. Mechanisms and functions of DNA mismatch repair. Cell Res 18:85–98. [PubMed]
138. Feng G, Tsui HC, Winkler ME. 1996. Depletion of the cellular amounts of the MutS and MutH methyl-directed mismatch repair proteins in stationary-phase Escherichia coli K-12 cells. J Bacteriol 178:2388–2396. [PubMed]
139. Tsui HC, Feng G, Winkler ME. 1997. Negative regulation of mutS and mutH repair gene expression by the Hfq and RpoS global regulators of Escherichia coli K-12. J Bacteriol 179:7476–7487. [PubMed]
140. Layton JC, Foster PL. 2003. Error-prone DNA polymerase IV is controlled by the stress-response σ factor, RpoS, in Escherichia coli. Mol Microbiol 50:549–561.
141. Barreto B, Rogers E, Xia J, Frisch RL, Richters M, Fitzgerald DM, Rosenberg SM. 2016. The small RNA GcvB promotes mutagenic break repair by opposing the membrane stress response. J Bacteriol 198:3296–3308. [PubMed]
142. Bordeau V, Felden B. 2014. Curli synthesis and biofilm formation in enteric bacteria are controlled by a dynamic small RNA module made up of a pseudoknot assisted by an RNA chaperone. Nucleic Acids Res 42:4682–4696. [PubMed]
Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.RWR-0022-2018
2018-07-06
2018-09-23

Abstract:

The ability of bacteria to thrive in diverse habitats and to adapt to ever-changing environmental conditions relies on the rapid and stringent modulation of gene expression. It has become evident in the past decade that small regulatory RNAs (sRNAs) are central components of networks controlling the bacterial responses to stress. Functioning at the posttranscriptional level, sRNAs base-pair with cognate mRNAs to alter translation, stability, or both to either repress or activate the targeted transcripts; the RNA chaperone Hfq participates in stabilizing sRNAs and in promoting pairing between target and sRNA. In particular, sRNAs act at the heart of crucial stress responses, including those dedicated to overcoming membrane damage and oxidative stress, discussed here. The bacterial cell envelope is the outermost protective barrier against the environment and thus is constantly monitored and remodeled. Here, we review the integration of sRNAs into the complex networks of several major envelope stress responses of Gram-negative bacteria, including the RpoE (σ), Cpx, and Rcs regulons. Oxidative stress, caused by bacterial respiratory activity or induced by toxic molecules, can lead to significant damage of cellular components. In and related bacteria, sRNAs also contribute significantly to the function of the RpoS (σ)-dependent general stress response as well as the specific OxyR- and SoxR/S-mediated responses to oxidative damage. Their activities in gene regulation and crosstalk to other stress-induced regulons are highlighted.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Activity of sRNAs in the general stress response. (A) Together with Hfq, the sRNAs DsrA, ArcZ, and RprA activate translation of the transcript by alleviating a self-inhibitory structure within the 5′ UTR of the mRNA. The sRNA OxyS functions as an indirect, negative regulator of expression. The major alternative sigma factor RpoS governs the general stress response and controls >400 genes in and related enterobacteria, including at least four sRNAs (SdsR, SdsN, GadY, and SraL). (B) Transcription factors which are restricted to function as either activators or repressors utilize sRNAs to facilitate opposite regulation.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0022-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

The role of sRNAs in the major envelope stress responses. Gram-negative bacteria are diderm, with the OM and IM being separated by the periplasmic space containing the PG cell wall. (A) OM homeostasis is regulated by the RpoE response. A series of proteolysis steps results in the degradation of the anti-sigma factor RseA and concomitant release of RpoE. The large regulon of the alternative sigma factor also comprises at least three sRNAs: MicA and RybB function to downregulate the transcripts of all major OMPs to reduce the accumulation of misfolded porins within the periplasm. MicL specifically represses translation of the mRNA. (B) Maintenance of the IM relies on the CpxA-CpxR TCS, which amongst other targets controls expression of at least three sRNAs, CyaR, RprA, and CpxQ. CpxQ is a stable fragment released by RNase E processing from the 3′ end of the mRNA. In association with Hfq, CpxQ functions to repress translation of several transcripts including mRNA, which encodes a periplasmic chaperone promoting the mistargeting of OMPs into the IM. (C) The IM-associated histidine kinase RcsC, phosphotransfer protein RcsD, and response regulator RcsB constitute the core of the Rcs system. The sRNA RprA is one highly induced component of the Rcs response, which is activated by LPS damage and perturbations of the cell wall. While acting as a negative regulator of the mRNA, RprA also promotes translation of both the and the messages. As transcription of (encoding an inhibitor of the conjugation machinery) is dependent on RpoS, RprA functions at the heart of a posttranscriptional feedforward loop for RicI activity.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0022-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Posttranscriptional regulation of LPS modification. The PhoQ-PhoP TCS, a major determinant of LPS modifications, is activated in response to Mg starvation as well as by AMPs. Translation of the bicistronic transcript is repressed by two sRNAs, MicA and GcvB. PhoQ-PhoP controls expression of MgrR, which, together with ArcZ, inhibits phosphoethanolamine (PEA) addition to the LPS oligosaccharide core by EptB. Both GcvB and MgrR are regulated at the posttranscriptional level by the sRNA SroC, which acts as a sponge and induces decay of its target sRNAs. Downregulation of mRNA by MicF decreases lipid A deacylation.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0022-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

The OxyS and MicF sRNAs are integrated into the enterobacterial response to oxidative stress. OxyS, induced by the hydrogen peroxide-responsive OxyR, downregulates mRNA (encoding a transcription factor regulating formate metabolism) and indirectly represses expression. In addition, OxyS-mediated repression of results in increased expression of , encoded in the cryptic Rac prophage. KilR sequesters FtsZ, thereby leading to inhibition of cell division and growth arrest, which allows the cell to facilitate DNA damage repair. MicF contributes to increased bacterial resistance against antibiotics of different classes by repressing the major porin OmpF. Additional targets of MicF include mRNA (encoding an LPS modification enzyme), as well as mRNA (encoding a transcriptional regulator of amino acid metabolism and transport). Expression of MicF is positively controlled by the transcription factors OmpR, MarA, Rob, and SoxS, with the last being induced in the presence of superoxide.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0022-2018
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error