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.

Global Regulation by CsrA and Its RNA Antagonists

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: Tony Romeo1, Paul Babitzke2
  • Editors: Gisela Storz4, Kai Papenfort5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611; 2: Department of Biochemistry and Molecular Biology; 3: Center for RNA Molecular Biology, The Pennsylvania State University, University Park, PA 16802; 4: Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; 5: Department of Biology I, Microbiology, LMU Munich, Martinsried, Germany
  • Source: microbiolspec March 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.RWR-0009-2017
  • Received 07 November 2017 Accepted 09 January 2018 Published 23 March 2018
  • Tony Romeo, tromeo@ufl.edu
image of Global Regulation by CsrA and Its RNA Antagonists
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Global Regulation by CsrA and Its RNA Antagonists, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/6/2/RWR-0009-2017-1.gif /docserver/preview/fulltext/microbiolspec/6/2/RWR-0009-2017-2.gif
  • Abstract:

    The sequence-specific RNA binding protein CsrA is employed by diverse bacteria in the posttranscriptional regulation of gene expression. Its binding interactions with RNA have been documented at atomic resolution and shown to alter RNA secondary structure, RNA stability, translation, and/or Rho-mediated transcription termination through a growing number of molecular mechanisms. In , small regulatory RNAs (sRNAs) that contain multiple CsrA binding sites compete with mRNA for binding to CsrA, thereby sequestering and antagonizing this protein. Both the synthesis and turnover of these sRNAs are regulated, allowing CsrA activity to be rapidly and efficiently adjusted in response to nutritional conditions and stresses. Feedback loops between the Csr regulatory components improve the dynamics of signal response by the Csr system. The Csr system of is intimately interconnected with other global regulatory systems, permitting it to contribute to regulation by those systems. In some species, a protein antagonist of CsrA functions as part of a checkpoint for flagellum biosynthesis. In other species, a protein antagonist participates in a mechanism in which a type III secretion system is used for sensing interactions with host cells. Recent transcriptomics studies reveal vast effects of CsrA on gene expression through direct binding to hundreds of mRNAs, and indirectly through its effects on the expression of dozens of transcription factors. CsrA binding to base-pairing sRNAs and novel mRNA segments, such as the 3′ untranslated region and deep within coding regions, predict its participation in yet-to-be-discovered regulatory mechanisms.

  • Citation: Romeo T, Babitzke P. 2018. Global Regulation by CsrA and Its RNA Antagonists. Microbiol Spectrum 6(2):RWR-0009-2017. doi:10.1128/microbiolspec.RWR-0009-2017.

References

1. Romeo T, Gong M, Liu MY, Brun-Zinkernagel AM. 1993. Identification and molecular characterization of csrA, a pleiotropic gene from Escherichia coli that affects glycogen biosynthesis, gluconeogenesis, cell size, and surface properties. J Bacteriol 175:4744–4755. [PubMed]
2. Babitzke P, Baker CS, Romeo T. 2009. Regulation of translation initiation by RNA binding proteins. Annu Rev Microbiol 63:27–44. [PubMed]
3. Vogel J, Luisi BF. 2011. Hfq and its constellation of RNA. Nat Rev Microbiol 9:578–589. [PubMed]
4. Updegrove TB, Zhang A, Storz G. 2016. Hfq: the flexible RNA matchmaker. Curr Opin Microbiol 30:133–138. [PubMed]
5. Dubey AK, Baker CS, Suzuki K, Jones AD, Pandit P, Romeo T, Babitzke P. 2003. CsrA regulates translation of the Escherichia coli carbon starvation gene, cstA, by blocking ribosome access to the cstA transcript. J Bacteriol 185:4450–4460. [PubMed]
6. Sabnis NA, Yang H, Romeo T. 1995. Pleiotropic regulation of central carbohydrate metabolism in Escherichia coli via the gene csrA. J Biol Chem 270:29096–29104. [PubMed]
7. Chatterjee A, Cui Y, Liu Y, Dumenyo CK, Chatterjee AK. 1995. Inactivation of rsmA leads to overproduction of extracellular pectinases, cellulases, and proteases in Erwinia carotovora subsp. Carotovora in the absence of the starvation/cell density-sensing signal, N-(3-oxohexanoyl)-l-homoserine lactone. Appl Environ Microbiol 61:1959–1967. [PubMed]
8. Altier C, Suyemoto M, Lawhon SD. 2000. Regulation of Salmonella enterica serovar Typhimurium invasion genes by csrA. Infect Immun 68:6790–6797. [PubMed]
9. Vakulskas CA, Potts AH, Babitzke P, Ahmer BMM, Romeo T. 2015. Regulation of bacterial virulence by Csr (Rsm) systems. Microbiol Mol Biol Rev 79:193–224. [PubMed]
10. Jackson DW, Suzuki K, Oakford L, Simecka JW, Hart ME, Romeo T. 2002. Biofilm formation and dispersal under the influence of the global regulator CsrA of Escherichia coli. J Bacteriol 184:290–301. [PubMed]
11. Wang X, Dubey AK, Suzuki K, Baker CS, Babitzke P, Romeo T. 2005. CsrA post-transcriptionally represses pgaABCD, responsible for synthesis of a biofilm polysaccharide adhesin of Escherichia coli. Mol Microbiol 56:1648–1663. [PubMed]
12. Jonas K, Edwards AN, Simm R, Romeo T, Römling U, Melefors O. 2008. The RNA binding protein CsrA controls cyclic di-GMP metabolism by directly regulating the expression of GGDEF proteins. Mol Microbiol 70:236–257. [PubMed]
13. Jonas K, Edwards AN, Ahmad I, Romeo T, Römling U, Melefors O. 2010. Complex regulatory network encompassing the Csr, c-di-GMP and motility systems of Salmonella Typhimurium. Environ Microbiol 12:524–540. [PubMed]
14. Pannuri A, Yakhnin H, Vakulskas CA, Edwards AN, Babitzke P, Romeo T. 2012. Translational repression of NhaR, a novel pathway for multi-tier regulation of biofilm circuitry by CsrA. J Bacteriol 194:79–89. [PubMed]
15. Yakhnin H, Baker CS, Berezin I, Evangelista MA, Rassin A, Romeo T, Babitzke P. 2011. CsrA represses translation of sdiA, which encodes the N-acylhomoserine-l-lactone receptor of Escherichia coli, by binding exclusively within the coding region of sdiA mRNA. J Bacteriol 193:6162–6170. [PubMed]
16. Yang H, Liu MY, Romeo T. 1996. Coordinate genetic regulation of glycogen catabolism and biosynthesis in Escherichia coli via the CsrA gene product. J Bacteriol 178:1012–1017. [PubMed]
17. Wei B, Shin S, LaPorte D, Wolfe AJ, Romeo T. 2000. Global regulatory mutations in csrA and rpoS cause severe central carbon stress in Escherichia coli in the presence of acetate. J Bacteriol 182:1632–1640. [PubMed]
18. Wei BL, Brun-Zinkernagel AM, Simecka JW, Prüss BM, Babitzke P, Romeo T. 2001. Positive regulation of motility and flhDC expression by the RNA-binding protein CsrA of Escherichia coli. Mol Microbiol 40:245–256. [PubMed]
19. Yakhnin AV, Baker CS, Vakulskas CA, Yakhnin H, Berezin I, Romeo T, Babitzke P. 2013. CsrA activates flhDC expression by protecting flhDC mRNA from Rnase E-mediated cleavage. Mol Microbiol 87:851–866. [PubMed]
20. Edwards AN, Patterson-Fortin LM, Vakulskas CA, Mercante JW, Potrykus K, Vinella D, Camacho MI, Fields JA, Thompson SA, Georgellis D, Cashel M, Babitzke P, Romeo T. 2011. Circuitry linking the Csr and stringent response global regulatory systems. Mol Microbiol 80:1561–1580. [PubMed]
21. Pannuri A, Vakulskas CA, Zere T, McGibbon LC, Edwards AN, Georgellis D, Babitzke P, Romeo T. 2016. Circuitry linking the catabolite repression and Csr global regulatory systems of Escherichia coli. J Bacteriol 198:3000–3015. [PubMed]
22. Park H, McGibbon LC, Potts AH, Yakhnin H, Romeo T, Babitzke P. 2017. Translational repression of the RpoS antiadapter IraD by CsrA is mediated via translational coupling to a short upstream open reading frame. MBio 4:e01355-17. doi:10.1128/mBio.01355-17.
23. Yakhnin H, Aichele R, Ades SE, Romeo T, Babitzke P. 2017. Circuitry linking the global Csr and σE-dependent cell envelope stress response systems. J Bacteriol 199:e00484-17. doi:10.1128/JB.00484-17.
24. Lawhon SD, Frye JG, Suyemoto M, Porwollik S, McClelland M, Altier C. 2003. Global regulation by CsrA in Salmonella typhimurium. Mol Microbiol 48:1633–1645. [PubMed]
25. Burrowes E, Baysse C, Adams C, O’Gara F. 2006. Influence of the regulatory protein RsmA on cellular functions in Pseudomonas aeruginosa PAO1, as revealed by transcriptome analysis. Microbiology 152:405–418. [PubMed]
26. Brencic A, McFarland KA, McManus HR, Castang S, Mogno I, Dove SL, Lory S. 2009. The GacS/GacA signal transduction system of Pseudomonas aeruginosa acts exclusively through its control over the transcription of the RsmY and RsmZ regulatory small RNAs. Mol Microbiol 73:434–445. [PubMed]
27. McKee AE, Rutherford BJ, Chivian DC, Baidoo EK, Juminaga D, Kuo D, Benke PI, Dietrich JA, Ma SM, Arkin AP, Petzold CJ, Adams PD, Keasling JD, Chhabra SR. 2012. Manipulation of the carbon storage regulator system for metabolite remodeling and biofuel production in Escherichia coli. Microb Cell Fact 11:79. doi:10.1186/1475-2859-11-79.
28. Tan Y, Liu ZY, Liu Z, Zheng HJ, Li FL. 2015. Comparative transcriptome analysis between csrA-disruption Clostridium acetobutylicum and its parent strain. Mol Biosyst 11:1434–1442. [PubMed]
29. Holmqvist E, Wright PR, Li L, Bischler T, Barquist L, Reinhardt R, Backofen R, Vogel J. 2016. Global RNA recognition patterns of post-transcriptional regulators Hfq and CsrA revealed by UV crosslinking in vivo. EMBO J 35:991–1011. [PubMed]
30. Fields JA, Li J, Gulbronson CJ, Hendrixson DR, Thompson SA. 2016. Campylobacter jejuni CsrA regulates metabolic and virulence associated proteins and is necessary for mouse colonization. PloS One 11:e0156932. doi:10.1371/journal.pone.0156932.
31. Dugar G, Svensson SL, Bischler T, Wäldchen S, Reinhardt R, Sauer M, Sharma CM. 2016. The CsrA-FliW network controls polar localization of the dual-function flagellin mRNA in Campylobacter jejuni. Nat Commun 7:11667. doi:10.1038/ncomms11667.
32. Morin M, Ropers D, Letisse F, Laguerre S, Portais JC, Cocaign-Bousquet M, Enjalbert B. 2016. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli. Mol Microbiol 100:686–700. [PubMed]
33. Sowa SW, Gelderman G, Leistra AN, Buvanendiran A, Lipp S, Pitaktong A, Vakulskas CA, Romeo T, Baldea M, Contreras LM. 2017. Integrative FourD omics approach profiles the target network of the carbon storage regulatory system. Nucleic Acids Res 45:1673–1686. [PubMed]
34. Sahr T, Rusniok C, Impens F, Oliva G, Sismeiro O, Coppée JY, Buchrieser C. 2017. The Legionella pneumophila genome evolved to accommodate multiple regulatory mechanisms controlled by the CsrA-system. PloS Genet 13:e1006629. doi:10.1371/journal.pgen.1006629.
35. Potts AH, Vakulskas CA, Pannuri A, Yakhnin H, Babitzke P, Romeo T. 2017. Global role of the bacterial post-transcriptional regulator CsrA revealed by integrated transcriptomics. Nat Commun 8:1596. doi:10.1038/s41467-017-01613-1.
36. Liu MY, Yang H, Romeo T. 1995. The product of the pleiotropic Escherichia coli gene csrA modulates glycogen biosynthesis via effects on mRNA stability. J Bacteriol 177:2663–2672. [PubMed]
37. Liu MY, Romeo T. 1997. The global regulator CsrA of Escherichia coli is a specific mRNA-binding protein. J Bacteriol 179:4639–4642. [PubMed]
38. Baker CS, Morozov I, Suzuki K, Romeo T, Babitzke P. 2002. CsrA regulates glycogen biosynthesis by preventing translation of glgC in Escherichia coli. Mol Microbiol 44:1599–1610. [PubMed]
39. Liu MY, Gui G, Wei B, Preston JF, III, Oakford L, Yüksel U, Giedroc DP, Romeo T. 1997. The RNA molecule CsrB binds to the global regulatory protein CsrA and antagonizes its activity in Escherichia coli. J Biol Chem 272:17502–17510. [PubMed]
40. Weilbacher T, Suzuki K, Dubey AK, Wang X, Gudapaty S, Morozov I, Baker CS, Georgellis D, Babitzke P, Romeo T. 2003. A novel sRNA component of the carbon storage regulatory system of Escherichia coli. Mol Microbiol 48:657–670. [PubMed]
41. Romeo T, Moore J, Smith J. 1991. A simple method for cloning genes involved in glucan biosynthesis: isolation of structural and regulatory genes for glycogen synthesis in Escherichia coli. Gene 108:23–29.
42. Dubey AK, Baker CS, Romeo T, Babitzke P. 2005. RNA sequence and secondary structure participate in high-affinity CsrA-RNA interaction. RNA 11:1579–1587. [PubMed]
43. Schulmeyer KH, Diaz MR, Bair TB, Sanders W, Gode CJ, Laederach A, Wolfgang MC, Yahr TL. 2016. Primary and secondary sequence structure requirements for recognition and discrimination of target RNAs by Pseudomonas aeruginosa RsmA and RsmF. J Bacteriol 198:2458–2469. [PubMed]
44. Gutiérrez P, Li Y, Osborne MJ, Pomerantseva E, Liu Q, Gehring K. 2005. Solution structure of the carbon storage regulator protein CsrA from Escherichia coli. J Bacteriol 187:3496–3501. [PubMed]
45. Heeb S, Kuehne SA, Bycroft M, Crivii S, Allen MD, Haas D, Cámara M, Williams P. 2006. Functional analysis of the post-transcriptional regulator RsmA reveals a novel RNA-binding site. J Mol Biol 355:1026–1036. [PubMed]
46. Schubert M, Lapouge K, Duss O, Oberstrass FC, Jelesarov I, Haas D, Allain FH-T. 2007. Molecular basis of messenger RNA recognition by the specific bacterial repressing clamp RsmA/CsrA. Nat Struct Mol Biol 14:807–813. [PubMed]
47. Altegoer F, Rensing SA, Bange G. 2016. Structural basis for the CsrA-dependent modulation of translation initiation by an ancient regulatory protein. Proc Natl Acad Sci U S A 113:10168–10173. [PubMed]
48. Mercante J, Suzuki K, Cheng X, Babitzke P, Romeo T. 2006. Comprehensive alanine-scanning mutagenesis of Escherichia coli CsrA defines two subdomains of critical functional importance. J Biol Chem 281:31832–31842. [PubMed]
49. Duss O, Michel E, Diarra dit Konté N, Schubert M, Allain FH. 2014. Molecular basis for the wide range of affinity found in Csr/Rsm protein-RNA recognition. Nucleic Acids Res 42:5332–5346. [PubMed]
50. Duss O, Michel E, Yulikov M, Schubert M, Jeschke G, Allain FH. 2014. Structural basis of the non-coding RNA RsmZ acting as a protein sponge. Nature 509:588–592. [PubMed]
51. Mercante J, Edwards AN, Dubey AK, Babitzke P, Romeo T. 2009. Molecular geometry of CsrA (RsmA) binding to RNA and its implications for regulated expression. J Mol Biol 392:511–528. [PubMed]
52. Yakhnin H, Yakhnin AV, Baker CS, Sineva E, Berezin I, Romeo T, Babitzke P. 2011. Complex regulation of the global regulatory gene csrA: CsrA-mediated translational repression, transcription from five promoters by Eσ70 and EσS, and indirect transcriptional activation by CsrA. Mol Microbiol 81:689–704. [PubMed]
53. Romeo T, Vakulskas CA, Babitzke P. 2013. Post-transcriptional regulation on a global scale: form and function of Csr/Rsm systems. Environ Microbiol 15:313–324. [PubMed]
54. Park H, Yakhnin H, Connolly M, Romeo T, Babitzke P. 2015. CsrA participates in a PNPase autoregulatory mechanism by selectively repressing translation of pnp transcripts that have been previously processed by Rnase III and PNPase. J Bacteriol 197:3751–3759. [PubMed]
55. Katsowich N, Elbaz N, Pal RR, Mills E, Kobi S, Kahan T, Rosenshine I. 2017. Host cell attachment elicits posttranscriptional regulation in infecting enteropathogenic bacteria. Science 355:735–739. [PubMed]
56. Yakhnin H, Pandit P, Petty TJ, Baker CS, Romeo T, Babitzke P. 2007. CsrA of Bacillus subtilis regulates translation initiation of the gene encoding the flagellin protein (hag) by blocking ribosome binding. Mol Microbiol 64:1605–1620. [PubMed]
57. Lapouge K, Sineva E, Lindell M, Starke K, Baker CS, Babitzke P, Haas D. 2007. Mechanism of hcnA mRNA recognition in the Gac/Rsm signal transduction pathway of Pseudomonas fluorescens. Mol Microbiol 66:341–356. [PubMed]
58. Martínez LC, Yakhnin H, Camacho MI, Georgellis D, Babitzke P, Puente JL, Bustamante VH. 2011. Integration of a complex regulatory cascade involving the SirA/BarA and Csr global regulatory systems that controls expression of the Salmonella SPI-1 and SPI-2 virulence regulons through HilD. Mol Microbiol 80:1637–1656. [PubMed]
59. Abbott ZD, Yakhnin H, Babitzke P, Swanson MS. 2015. csrR, a paralog and direct target of CsrA, promotes Legionella pneumophila resilience in water. mBio 6:e00595. doi:10.1128/mBio.00595-15.
60. Irie Y, Starkey M, Edwards AN, Wozniak DJ, Romeo T, Parsek MR. 2010. Pseudomonas aeruginosa biofilm matrix polysaccharide Psl is regulated transcriptionally by RpoS and post-transcriptionally by RsmA. Mol Microbiol 78:158–172.
61. Baker CS, Eöry LA, Yakhnin H, Mercante J, Romeo T, Babitzke P. 2007. CsrA inhibits translation initiation of Escherichia coli hfq by binding to a single site overlapping the Shine-Dalgarno sequence. J Bacteriol 189:5472–5481. [PubMed]
62. Figueroa-Bossi N, Schwartz A, Guillemardet B, D’Heygère F, Bossi L, Boudvillain M. 2014. RNA remodeling by bacterial global regulator CsrA promotes Rho-dependent transcription termination. Genes Dev 28:1239–1251. [PubMed]
63. Goller C, Wang X, Itoh Y, Romeo T. 2006. The cation-responsive protein NhaR of Escherichia coli activates pgaABCD transcription, required for production of the biofilm adhesin poly-β-1,6-N-acetyl-d-glucosamine. J Bacteriol 188:8022–8032. [PubMed]
64. Steiner S, Lori C, Boehm A, Jenal U. 2013. Allosteric activation of exopolysaccharide synthesis through cyclic di-GMP-stimulated protein-protein interaction. EMBO J 32:354–368. [PubMed]
65. Patterson-Fortin LM, Vakulskas CA, Yakhnin H, Babitzke P, Romeo T. 2013. Dual posttranscriptional regulation via a cofactor-responsive mRNA leader. J Mol Biol 425:3662–3677. [PubMed]
66. Ren B, Shen H, Lu ZJ, Liu H, Xu Y. 2014. The phzA2-G2 transcript exhibits direct RsmA-mediated activation in Pseudomonas aeruginosa M18. PloS One 9:e89653. doi:10.1371/journal.pone.0089653.
67. Liu Y, Cui Y, Mukherjee A, Chatterjee AK. 1998. Characterization of a novel RNA regulator of Erwinia carotovora ssp. Carotovora that controls production of extracellular enzymes and secondary metabolites. Mol Microbiol 29:219–234. [PubMed]
68. Zere TR, Vakulskas CA, Leng Y, Pannuri A, Potts AH, Dias R, Tang D, Kolaczkowski B, Georgellis D, Ahmer BM, Romeo T. 2015. Genomic targets and features of BarA-UvrY (-SirA) signal transduction systems. PloS One 10:e0145035. doi:10.1371/journal.pone.0145035.
69. Kay E, Dubuis C, Haas D. 2005. Three small RNAs jointly ensure secondary metabolism and biocontrol in Pseudomonas fluorescens CHA0. Proc Natl Acad Sci U S A 102:17136–17141. [PubMed]
70. Lenz DH, Miller MB, Zhu J, Kulkarni RV, Bassler BL. 2005. CsrA and three redundant small RNAs regulate quorum sensing in Vibrio cholerae. Mol Microbiol 58:1186–1202. [PubMed]
71. Kay E, Humair B, Dénervaud V, Riedel K, Spahr S, Eberl L, Valverde C, Haas D. 2006. Two GacA-dependent small RNAs modulate the quorum-sensing response in Pseudomonas aeruginosa. J Bacteriol 188:6026–6033. [PubMed]
72. Teplitski M, Al-Agely A, Ahmer BM. 2006. Contribution of the SirA regulon to biofilm formation in Salmonella enterica serovar Typhimurium. Microbiology 152:3411–3424. [PubMed]
73. Fortune DR, Suyemoto M, Altier C. 2006. Identification of CsrC and characterization of its role in epithelial cell invasion in Salmonella enterica serovar Typhimurium. Infect Immun 74:331–339. [PubMed]
74. Sterzenbach T, Nguyen KT, Nuccio SP, Winter MG, Vakulskas CA, Clegg S, Romeo T, Bäumler AJ. 2013. A novel CsrA titration mechanism regulates fimbrial gene expression in Salmonella typhimurium. EMBO J 32:2872–2883. [PubMed]
75. Jørgensen MG, Thomason MK, Havelund J, Valentin-Hansen P, Storz G. 2013. Dual function of the McaS small RNA in controlling biofilm formation. Genes Dev 27:1132–1145. [PubMed]
76. Parker A, Cureoglu S, De Lay N, Majdalani N, Gottesman S. 2017. Alternative pathways for Escherichia coli biofilm formation revealed by sRNA overproduction. Mol Microbiol 105:309–325. [PubMed]
77. Itoh Y, Rice JD, Goller C, Pannuri A, Taylor J, Meisner J, Beveridge TJ, Preston JF, III, Romeo T. 2008. Roles of pgaABCD genes in synthesis, modification, and export of the Escherichia coli biofilm adhesin poly-β-1,6-N-acetyl-d-glucosamine. J Bacteriol 190:3670–3680. [PubMed]
78. Mukherjee S, Yakhnin H, Kysela D, Sokoloski J, Babitzke P, Kearns DB. 2011. CsrA-FliW interaction governs flagellin homeostasis and a checkpoint on flagellar morphogenesis in Bacillus subtilis. Mol Microbiol 82:447–461. [PubMed]
79. Mukherjee S, Oshiro RT, Yakhnin H, Babitzke P, Kearns DB. 2016. FliW antagonizes CsrA RNA binding by a noncompetitive allosteric mechanism. Proc Natl Acad Sci U S A 113:9870–9875. [PubMed]
80. Bhatt S, Edwards AN, Nguyen HT, Merlin D, Romeo T, Kalman D. 2009. The RNA binding protein CsrA is a pleiotropic regulator of the locus of enterocyte effacement pathogenicity island of enteropathogenic Escherichia coli. Infect Immun 77:3552–3568. [PubMed]
81. Pernestig AK, Melefors O, Georgellis D. 2001. Identification of UvrY as the cognate response regulator for the BarA sensor kinase in Escherichia coli. J Biol Chem 276:225–231. [PubMed]
82. Suzuki K, Wang X, Weilbacher T, Pernestig AK, Melefors O, Georgellis D, Babitzke P, Romeo T. 2002. Regulatory circuitry of the CsrA/CsrB and BarA/UvrY systems of Escherichia coli. J Bacteriol 184:5130–5140. [PubMed]
83. Heroven AK, Sest M, Pisano F, Scheb-Wetzel M, Steinmann R, Böhme K, Klein J, Münch R, Schomburg D, Dersch P. 2012. Crp induces switching of the CsrB and CsrC RNAs in Yersinia pseudotuberculosis and links nutritional status to virulence. Front Cell Infect Microbiol 2:158. doi:10.3389/fcimb.2012.00158.
84. Tomenius H, Pernestig AK, Méndez-Catalá CF, Georgellis D, Normark S, Melefors O. 2005. Genetic and functional characterization of the Escherichia coli BarA-UvrY two-component system: point mutations in the HAMP linker of the BarA sensor give a dominant-negative phenotype. J Bacteriol 187:7317–7324. [PubMed]
85. Chavez RG, Alvarez AF, Romeo T, Georgellis D. 2010. The physiological stimulus for the BarA sensor kinase. J Bacteriol 192:2009–2012. [PubMed]
86. Lawhon SD, Maurer R, Suyemoto M, Altier C. 2002. Intestinal short-chain fatty acids alter Salmonella typhimurium invasion gene expression and virulence through BarA/SirA. Mol Microbiol 46:1451–1464. [PubMed]
87. Takeuchi K, Kiefer P, Reimmann C, Keel C, Dubuis C, Rolli J, Vorholt JA, Haas D. 2009. Small RNA-dependent expression of secondary metabolism is controlled by Krebs cycle function in Pseudomonas fluorescens. J Biol Chem 284:34976–34985. [PubMed]
88. Septer AN, Bose JL, Lipzen A, Martin J, Whistler C, Stabb EV. 2015. Bright luminescence of Vibrio fischeri aconitase mutants reveals a connection between citrate and the Gac/Csr regulatory system. Mol Microbiol 95:283–296. [PubMed]
89. Vakulskas CA, Pannuri A, Cortés-Selva D, Zere TR, Ahmer BM, Babitzke P, Romeo T. 2014. Global effects of the DEAD-box RNA helicase DeaD (CsdA) on gene expression over a broad range of temperatures. Mol Microbiol 92:945–958. [PubMed]
90. Camacho MI, Alvarez AF, Chavez RG, Romeo T, Merino E, Georgellis D. 2015. Effects of the global regulator CsrA on the BarA/UvrY two-component signaling system. J Bacteriol 197:983–991. [PubMed]
91. Potrykus K, Cashel M. 2008. (p)ppGpp: still magical? Annu Rev Microbiol 62:35–51. [PubMed]
92. Ross W, Sanchez-Vazquez P, Chen AY, Lee JH, Burgos HL, Gourse RL. 2016. ppGpp binding to a site at the RNAP-DksA interface accounts for its dramatic effects on transcription initiation during the stringent response. Mol Cell 62:811–823. [PubMed]
93. Chambonnier G, Roux L, Redelberger D, Fadel F, Filloux A, Sivaneson M, de Bentzmann S, Bordi C. 2016. The hybrid histidine kinase LadS forms a multicomponent signal transduction system with the GacS/GacA two-component system in Pseudomonas aeruginosa. PloS Genet 12:e1006032. doi:10.1371/journal.pgen.1006032.
94. Suzuki K, Babitzke P, Kushner SR, Romeo T. 2006. Identification of a novel regulatory protein (CsrD) that targets the global regulatory RNAs CsrB and CsrC for degradation by Rnase E. Genes Dev 20:2605–2617. [PubMed]
95. Gudapaty S, Suzuki K, Wang X, Babitzke P, Romeo T. 2001. Regulatory interactions of Csr components: the RNA binding protein CsrA activates csrB transcription in Escherichia coli. J Bacteriol 183:6017–6027. [PubMed]
96. Vakulskas CA, Leng Y, Abe H, Amaki T, Okayama A, Babitzke P, Suzuki K, Romeo T. 2016. Antagonistic control of the turnover pathway for the global regulatory sRNA CsrB by the CsrA and CsrD proteins. Nucleic Acids Res 44:7896–7910. [PubMed]
97. Leng Y, Vakulskas CA, Zere TR, Pickering BS, Watnick PI, Babitzke P, Romeo T. 2016. Regulation of CsrB/C sRNA decay by EIIA(Glc) of the phosphoenolpyruvate: carbohydrate phosphotransferase system. Mol Microbiol 99:627–639. [PubMed]
98. Valverde C, Lindell M, Wagner EG, Haas D. 2004. A repeated GGA motif is critical for the activity and stability of the riboregulator RsmY of Pseudomonas fluorescens. J Biol Chem 279:25066–25074. [PubMed]
99. Alon U. 2007. Network motifs: theory and experimental approaches. Nat Rev Genet 8:450–461. [PubMed]
100. Beisel CL, Storz G. 2010. Base pairing small RNAs and their roles in global regulatory networks. FEMS Microbiol Rev 34:866–882. [PubMed]
101. Adamson DN, Lim HN. 2013. Rapid and robust signaling in the CsrA cascade via RNA-protein interactions and feedback regulation. Proc Natl Acad Sci U S A 110:13120–13125. [PubMed]
102. Heroven AK, Böhme K, Dersch P. 2012. The Csr/Rsm system of Yersinia and related pathogens: a post-transcriptional strategy for managing virulence. RNA Biol 9:379–391. [PubMed]
103. Svenningsen SL, Tu KC, Bassler BL. 2009. Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing. EMBO J 28:429–439. [PubMed]
104. Cui Y, Madi L, Mukherjee A, Dumenyo CK, Chatterjee AK. 1996. The RsmA mutants of Erwinia carotovora subsp. Carotovora strain Ecc71 overexpress hrpNEcc and elicit a hypersensitive reaction-like response in tobacco leaves. Mol Plant Microbe Interact 9:565–573. [PubMed]
105. Chandrangsu P, Lemke JJ, Gourse RL. 2011. The dksA promoter is negatively feedback regulated by DksA and ppGpp. Mol Microbiol 80:1337–1348. [PubMed]
106. 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.
107. 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.
108. Shimada T, Tanaka K, Ishihama A. 2017. The whole set of the constitutive promoters recognized by four minor sigma subunits of Escherichia coli RNA polymerase. PloS One 12:e0179181. doi:10.1371/journal.pone.0179181.
109. Gopalkrishnan S, Nicoloff H, Ades SE. 2014. Co-ordinated regulation of the extracytoplasmic stress factor, sigmaE, with other Escherichia coli sigma factors by (p)ppGpp and DksA may be achieved by specific regulation of individual holoenzymes. Mol Microbiol 93:479–493. [PubMed]
110. Deutscher J, Aké FM, Derkaoui M, Zébré AC, Cao TN, Bouraoui H, Kentache T, Mokhtari A, Milohanic E, Joyet P. 2014. The bacterial phosphoenolpyruvate:carbohydrate phosphotransferase system: regulation by protein phosphorylation and phosphorylation-dependent protein-protein interactions. Microbiol Mol Biol Rev 78:231–256. [PubMed]
111. Shimada T, Fujita N, Yamamoto K, Ishihama A. 2011. Novel roles of cAMP receptor protein (CRP) in regulation of transport and metabolism of carbon sources. PloS One 6:e20081. doi:10.1371/journal.pone.0020081.
112. Lee DJ, Busby SJ. 2012. Repression by cyclic AMP receptor protein at a distance. mBio 3:e00289-12. doi:10.1128/mBio.00289-12.
113. You C, Okano H, Hui S, Zhang Z, Kim M, Gunderson CW, Wang YP, Lenz P, Yan D, Hwa T. 2013. Coordination of bacterial proteome with metabolism by cyclic AMP signaling. Nature 500:301–306. [PubMed]
Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.RWR-0009-2017
2018-03-23
2018-04-25

Abstract:

The sequence-specific RNA binding protein CsrA is employed by diverse bacteria in the posttranscriptional regulation of gene expression. Its binding interactions with RNA have been documented at atomic resolution and shown to alter RNA secondary structure, RNA stability, translation, and/or Rho-mediated transcription termination through a growing number of molecular mechanisms. In , small regulatory RNAs (sRNAs) that contain multiple CsrA binding sites compete with mRNA for binding to CsrA, thereby sequestering and antagonizing this protein. Both the synthesis and turnover of these sRNAs are regulated, allowing CsrA activity to be rapidly and efficiently adjusted in response to nutritional conditions and stresses. Feedback loops between the Csr regulatory components improve the dynamics of signal response by the Csr system. The Csr system of is intimately interconnected with other global regulatory systems, permitting it to contribute to regulation by those systems. In some species, a protein antagonist of CsrA functions as part of a checkpoint for flagellum biosynthesis. In other species, a protein antagonist participates in a mechanism in which a type III secretion system is used for sensing interactions with host cells. Recent transcriptomics studies reveal vast effects of CsrA on gene expression through direct binding to hundreds of mRNAs, and indirectly through its effects on the expression of dozens of transcription factors. CsrA binding to base-pairing sRNAs and novel mRNA segments, such as the 3′ untranslated region and deep within coding regions, predict its participation in yet-to-be-discovered regulatory mechanisms.

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

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

(A) Example of a high-affinity CsrA binding site. The conserved GGA motif is in red. (B) Structure of the CsrA-RNA complex. The GGA motifs are indicated by blue boxes, and the critical L4 and R44 residues are indicated in red. Adapted from reference 46 with permission.

Source: microbiolspec March 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.RWR-0009-2017
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Mechanisms for CsrA-mediated translational repression (A), transcription termination (B), and protection of mRNA from nuclease cleavage. Adapted from reference 9 with permission.

Source: microbiolspec March 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.RWR-0009-2017
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Modes of CsrA antagonism. In various species, dedicated sRNAs, moonlighting sRNAs, mRNA, and/or proteins have been found to bind to CsrA and inhibit its activity.

Source: microbiolspec March 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.RWR-0009-2017
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

Central regulatory circuitry of the Csr system. Dedicated components of the Csr system are highlighted in red.

Source: microbiolspec March 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.RWR-0009-2017
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5
FIGURE 5

Regulatory interactions of the Csr system with stringent response (A), extracytoplasmic stress (B), and carbon catabolite repression (C) global regulatory systems. Adapted from references 20 , 21 , and 23 with permission.

Source: microbiolspec March 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.RWR-0009-2017
Permissions and Reprints Request Permissions
Download as Powerpoint

Tables

Generic image for table
TABLE 1

CsrA and its antagonists

Source: microbiolspec March 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.RWR-0009-2017

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