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Noncoding RNA

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  • Authors: E. Desgranges1, S. Marzi2, K. Moreau3, P. Romby4, I. Caldelari5
  • Editors: Vincent A. Fischetti6, Richard P. Novick7, Joseph J. Ferretti8, Daniel A. Portnoy9, Miriam Braunstein10, Julian I. Rood11
    Affiliations: 1: Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, F-67000 Strasbourg, France; 2: Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, F-67000 Strasbourg, France; 3: CIRI, International Center for Infectiology Research, Inserm, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Hospices Civils de Lyon, University of Lyon, F-69008, Lyon, France; 4: Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, F-67000 Strasbourg, France; 5: Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, F-67000 Strasbourg, France; 6: The Rockefeller University, New York, NY; 7: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 8: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 9: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 10: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 11: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0038-2018
  • Received 07 August 2018 Accepted 25 October 2018 Published 19 April 2019
  • Isabelle Caldelari, [email protected]
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  • Abstract:

    Regulatory RNAs, present in many bacterial genomes and particularly in pathogenic bacteria such as , control the expression of genes encoding virulence factors or metabolic proteins. They are extremely diverse and include noncoding RNAs (sRNA), antisense RNAs, and some 5′ or 3′ untranslated regions of messenger RNAs that act as sensors for metabolites, tRNAs, or environmental conditions (e.g., temperature, pH). In this review we focus on specific examples of sRNAs of that illustrate how numerous sRNAs and associated proteins are embedded in complex networks of regulation. In addition, we discuss the CRISPR-Cas systems defined as an RNA-interference-like mechanism, which also exist in staphylococcal strains.

  • Citation: Desgranges E, Marzi S, Moreau K, Romby P, Caldelari I. 2019. Noncoding RNA. Microbiol Spectrum 7(2):GPP3-0038-2018. doi:10.1128/microbiolspec.GPP3-0038-2018.


1. Bischoff M, Romby P. 2016. Genetic regulation, p 301–334. In Staphylococcus: Genetics and Physiology. Caister Academic Press, Poole, United Kingdom. [PubMed]
2. Tomasini A, François P, Howden BP, Fechter P, Romby P, Caldelari I. 2014. The importance of regulatory RNAs in Staphylococcus aureus. Infect Genet Evol 21:616–626 http://dx.doi.org/10.1016/j.meegid.2013.11.016.
3. Guillet J, Hallier M, Felden B. 2013. Emerging functions for the Staphylococcus aureus RNome. PLoS Pathog 9:e1003767 http://dx.doi.org/10.1371/journal.ppat.1003767. [PubMed]
4. Caldelari I, Fechter P, Lioliou E, Romilly C, Chevalier C, Gaspin C, Romby P. 2011. A current overview of regulatory RNAs in Staphylococcus aureus, p 51–75. In Marchfelder A, Hess W (ed), Regulatory RNAs in Prokaryotes. Springer-Verlag, Vienna, Austria.
5. Quereda JJ, Cossart P. 2017. Regulating bacterial virulence with RNA. Annu Rev Microbiol 71:263–280 http://dx.doi.org/10.1146/annurev-micro-030117-020335. [PubMed]
6. Mulhbacher J, Brouillette E, Allard M, Fortier L-C, Malouin F, Lafontaine DA. 2010. Novel riboswitch ligand analogs as selective inhibitors of guanine-related metabolic pathways. PLoS Pathog 6:e1000865 http://dx.doi.org/10.1371/journal.ppat.1000865. [PubMed]
7. Lünse CE, Schmidt MS, Wittmann V, Mayer G. 2011. Carba-sugars activate the glmS-riboswitch of Staphylococcus aureus. ACS Chem Biol 6:675–678 http://dx.doi.org/10.1021/cb200016d. [PubMed]
8. Collins JA, Irnov I, Baker S, Winkler WC. 2007. Mechanism of mRNA destabilization by the glmS ribozyme. Genes Dev 21:3356–3368 http://dx.doi.org/10.1101/gad.1605307. [PubMed]
9. Dar D, Shamir M, Mellin JR, Koutero M, Stern-Ginossar N, Cossart P, Sorek R. 2016. Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria. Science 352:aad9822 http://dx.doi.org/10.1126/science.aad9822. [PubMed]
10. Apostolidi M, Saad NY, Drainas D, Pournaras S, Becker HD, Stathopoulos C. 2015. A glyS T-box riboswitch with species-specific structural features responding to both proteinogenic and nonproteinogenic tRNA Gly isoacceptors. RNA 21:1790–1806 http://dx.doi.org/10.1261/rna.052712.115. [PubMed]
11. Stamatopoulou V, Apostolidi M, Li S, Lamprinou K, Papakyriakou A, Zhang J, Stathopoulos C. 2017. Direct modulation of T-box riboswitch-controlled transcription by protein synthesis inhibitors. Nucleic Acids Res 45:10242–10258 http://dx.doi.org/10.1093/nar/gkx663. [PubMed]
12. Kortmann J, Narberhaus F. 2012. Bacterial RNA thermometers: molecular zippers and switches. Nat Rev Microbiol 10:255–265 http://dx.doi.org/10.1038/nrmicro2730. [PubMed]
13. Johansson J, Mandin P, Renzoni A, Chiaruttini C, Springer M, Cossart P. 2002. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110:551–561 http://dx.doi.org/10.1016/S0092-8674(02)00905-4.
14. Loh E, Memarpour F, Vaitkevicius K, Kallipolitis BH, Johansson J, Sondén B. 2012. An unstructured 5′-coding region of the prfA mRNA is required for efficient translation. Nucleic Acids Res 40:1818–1827 http://dx.doi.org/10.1093/nar/gkr850. [PubMed]
15. Lasa I, Toledo-Arana A, Gingeras TR. 2012. An effort to make sense of antisense transcription in bacteria. RNA Biol 9:1039–1044 http://dx.doi.org/10.4161/rna.21167. [PubMed]
16. Ruiz de los Mozos I, Vergara-Irigaray M, Segura V, Villanueva M, Bitarte N, Saramago M, Domingues S, Arraiano CM, Fechter P, Romby P, Valle J, Solano C, Lasa I, Toledo-Arana A. 2013. Base pairing interaction between 5′- and 3′-UTRs controls icaR mRNA translation in Staphylococcus aureus. PLoS Genet 9:e1004001 http://dx.doi.org/10.1371/journal.pgen.1004001. [PubMed]
17. 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 http://dx.doi.org/10.1038/emboj.2012.229. [PubMed]
18. 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 http://dx.doi.org/10.1016/j.molcel.2015.12.023. [PubMed]
19. 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 http://dx.doi.org/10.15252/embj.201490546. [PubMed]
20. Fozo EM, Hemm MR, Storz G. 2008. Small toxic proteins and the antisense RNAs that repress them. Microbiol Mol Biol Rev 72:579–589 http://dx.doi.org/10.1128/MMBR.00025-08. [PubMed]
21. Novick RP, Iordanescu S, Projan SJ, Kornblum J, Edelman I. 1989. pT181 plasmid replication is regulated by a countertranscript-driven transcriptional attenuator. Cell 59:395–404 http://dx.doi.org/10.1016/0092-8674(89)90300-0.
22. Lasa I, Toledo-Arana A, Dobin A, Villanueva M, de los Mozos IR, Vergara-Irigaray M, Segura V, Fagegaltier D, Penadés JR, Valle J, Solano C, Gingeras TR. 2011. Genome-wide antisense transcription drives mRNA processing in bacteria. Proc Natl Acad Sci U S A 108:20172–20177 http://dx.doi.org/10.1073/pnas.1113521108. [PubMed]
23. Lioliou E, Sharma CM, Caldelari I, Helfer A-C, Fechter P, Vandenesch F, Vogel J, Romby P. 2012. Global regulatory functions of the Staphylococcus aureus endoribonuclease III in gene expression. PLoS Genet 8:e1002782 http://dx.doi.org/10.1371/journal.pgen.1002782. [PubMed]
24. Bidnenko V, Nicolas P, Grylak-Mielnicka A, Delumeau O, Auger S, Aucouturier A, Guerin C, Repoila F, Bardowski J, Aymerich S, Bidnenko E. 2017. Termination factor Rho: from the control of pervasive transcription to cell fate determination in Bacillus subtilis. PLoS Genet 13:e1006909 http://dx.doi.org/10.1371/journal.pgen.1006909. [PubMed]
25. Mäder U, Nicolas P, Depke M, Pané-Farré J, Debarbouille M, van der Kooi-Pol MM, Guérin C, Dérozier S, Hiron A, Jarmer H, Leduc A, Michalik S, Reilman E, Schaffer M, Schmidt F, Bessières P, Noirot P, Hecker M, Msadek T, Völker U, van Dijl JM. 2016. Staphylococcus aureus transcriptome architecture: from laboratory to infection-mimicking conditions. PLoS Genet 12:e1005962 http://dx.doi.org/10.1371/journal.pgen.1005962. [PubMed]
26. Goeders N, Chai R, Chen B, Day A, Salmond GP. 2016. Structure, evolution, and functions of bacterial type III toxin-antitoxin systems. Toxins (Basel) 8:282 http://dx.doi.org/10.3390/toxins8100282. [PubMed]
27. Coray DS, Wheeler NE, Heinemann JA, Gardner PP. 2017. Why so narrow: distribution of anti-sense regulated, type I toxin-antitoxin systems compared with type II and type III systems. RNA Biol 14:275–280 http://dx.doi.org/10.1080/15476286.2016.1272747. [PubMed]
28. Brielle R, Pinel-Marie M-L, Felden B. 2016. Linking bacterial type I toxins with their actions. Curr Opin Microbiol 30:114–121 http://dx.doi.org/10.1016/j.mib.2016.01.009. [PubMed]
29. Pinel-Marie M-L, Brielle R, Felden B. 2014. Dual toxic-peptide-coding Staphylococcus aureus RNA under antisense regulation targets host cells and bacterial rivals unequally. Cell Reports 7:424–435 http://dx.doi.org/10.1016/j.celrep.2014.03.012. [PubMed]
30. Sayed N, Jousselin A, Felden B. 2011. A cis-antisense RNA acts in trans in Staphylococcus aureus to control translation of a human cytolytic peptide. Nat Struct Mol Biol 19:105–112 http://dx.doi.org/10.1038/nsmb.2193. [PubMed]
31. Bronsard J, Pascreau G, Sassi M, Mauro T, Augagneur Y, Felden B. 2017. sRNA and cis-antisense sRNA identification in Staphylococcus aureus highlights an unusual sRNA gene cluster with one encoding a secreted peptide. Sci Rep 7:4565 http://dx.doi.org/10.1038/s41598-017-04786-3. [PubMed]
32. Neubauer C, Gao Y-G, Andersen KR, Dunham CM, Kelley AC, Hentschel J, Gerdes K, Ramakrishnan V, Brodersen DE. 2009. The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE. Cell 139:1084–1095 http://dx.doi.org/10.1016/j.cell.2009.11.015. [PubMed]
33. Berghoff BA, Wagner EGH. 2017. RNA-based regulation in type I toxin-antitoxin systems and its implication for bacterial persistence. Curr Genet 63:1011–1016 http://dx.doi.org/10.1007/s00294-017-0710-y. [PubMed]
34. Updegrove TB, Zhang A, Storz G. 2016. Hfq: the flexible RNA matchmaker. Curr Opin Microbiol 30:133–138 http://dx.doi.org/10.1016/j.mib.2016.02.003. [PubMed]
35. Attaiech L, Glover JNM, Charpentier X. 2017. RNA chaperones step out of Hfq’s shadow. Trends Microbiol 25:247–249 http://dx.doi.org/10.1016/j.tim.2017.01.006. [PubMed]
36. Zheng A, Panja S, Woodson SA. 2016. Arginine patch predicts the RNA annealing activity of Hfq from Gram-negative and Gram-positive bacteria. J Mol Biol 428:2259–2264 http://dx.doi.org/10.1016/j.jmb.2016.03.027. [PubMed]
37. Bronesky D, Wu Z, Marzi S, Walter P, Geissmann T, Moreau K, Vandenesch F, Caldelari I, Romby P. 2016. Staphylococcus aureus RNAIII and its regulon link quorum sensing, stress responses, metabolic adaptation, and regulation of virulence gene expression. Annu Rev Microbiol 70:299–316 http://dx.doi.org/10.1146/annurev-micro-102215-095708. [PubMed]
38. Xue T, Zhang X, Sun H, Sun B. 2014. ArtR, a novel sRNA of Staphylococcus aureus, regulates α-toxin expression by targeting the 5′ UTR of sarT mRNA. Med Microbiol Immunol (Berl) 203:1–12 http://dx.doi.org/10.1007/s00430-013-0307-0. [PubMed]
39. Geissmann T, Chevalier C, Cros M-J, Boisset S, Fechter P, Noirot C, Schrenzel J, François P, Vandenesch F, Gaspin C, Romby P. 2009. A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation. Nucleic Acids Res 37:7239–7257 http://dx.doi.org/10.1093/nar/gkp668. [PubMed]
40. Mauro T, Rouillon A, Felden B. 2016. Insights into the regulation of small RNA expression: SarA represses the expression of two sRNAs in Staphylococcus aureus. Nucleic Acids Res 44:10186–10200.
41. Le Pabic H, Germain-Amiot N, Bordeau V, Felden B. 2015. A bacterial regulatory RNA attenuates virulence, spread and human host cell phagocytosis. Nucleic Acids Res 43:9232–9248 http://dx.doi.org/10.1093/nar/gkv783. [PubMed]
42. Bohn C, Rigoulay C, Chabelskaya S, Sharma CM, Marchais A, Skorski P, Borezée-Durant E, Barbet R, Jacquet E, Jacq A, Gautheret D, Felden B, Vogel J, Bouloc P. 2010. Experimental discovery of small RNAs in Staphylococcus aureus reveals a riboregulator of central metabolism. Nucleic Acids Res 38:6620–6636 http://dx.doi.org/10.1093/nar/gkq462. [PubMed]
43. Durand S, Tomasini A, Braun F, Condon C, Romby P. 2015. sRNA and mRNA turnover in Gram-positive bacteria. FEMS Microbiol Rev 39:316–330 http://dx.doi.org/10.1093/femsre/fuv007. [PubMed]
44. Durand S, Braun F, Helfer A-C, Romby P, Condon C. 2017. sRNA-mediated activation of gene expression by inhibition of 5′-3′ exonucleolytic mRNA degradation. eLife 6:e23602 http://dx.doi.org/10.7554/eLife.23602. [PubMed]
45. Nielsen JS, Christiansen MHG, Bonde M, Gottschalk S, Frees D, Thomsen LE, Kallipolitis BH. 2011. Searching for small σB-regulated genes in Staphylococcus aureus. Arch Microbiol 193:23–34 http://dx.doi.org/10.1007/s00203-010-0641-1. [PubMed]
46. Marincola G, Schäfer T, Behler J, Bernhardt J, Ohlsen K, Goerke C, Wolz C. 2012. RNase Y of Staphylococcus aureus and its role in the activation of virulence genes. Mol Microbiol 85:817–832 http://dx.doi.org/10.1111/j.1365-2958.2012.08144.x. [PubMed]
47. Romilly C, Lays C, Tomasini A, Caldelari I, Benito Y, Hammann P, Geissmann T, Boisset S, Romby P, Vandenesch F. 2014. A non-coding RNA promotes bacterial persistence and decreases virulence by regulating a regulator in Staphylococcus aureus. PLoS Pathog 10:e1003979 http://dx.doi.org/10.1371/journal.ppat.1003979. [PubMed]
48. Tomasini A, Moreau K, Chicher J, Geissmann T, Vandenesch F, Romby P, Marzi S, Caldelari I. 2017. The RNA targetome of Staphylococcus aureus non-coding RNA RsaA: impact on cell surface properties and defense mechanisms. Nucleic Acids Res 45:6746–6760 http://dx.doi.org/10.1093/nar/gkx219. [PubMed]
49. Beaume M, Hernandez D, Farinelli L, Deluen C, Linder P, Gaspin C, Romby P, Schrenzel J, Francois P. 2010. Cartography of methicillin-resistant S. aureus transcripts: detection, orientation and temporal expression during growth phase and stress conditions. PLoS One 5:e10725 http://dx.doi.org/10.1371/journal.pone.0010725. [PubMed]
50. Kim S, Reyes D, Beaume M, Francois P, Cheung A. 2014. Contribution of teg49 small RNA in the 5′ upstream transcriptional region of sarA to virulence in Staphylococcus aureus. Infect Immun 82:4369–4379 http://dx.doi.org/10.1128/IAI.02002-14. [PubMed]
51. Manna AC, Kim S, Cengher L, Corvaglia A, Leo S, Francois P, Cheung AL. 2018. Small RNA teg49 Is derived from a sarA transcript and regulates virulence genes independent of SarA in Staphylococcus aureus. Infect Immun 86:e00635-17. [PubMed]
52. Labrie SJ, Samson JE, Moineau S. 2010. Bacteriophage resistance mechanisms. Nat Rev Microbiol 8:317–327 http://dx.doi.org/10.1038/nrmicro2315. [PubMed]
53. Westra ER, Swarts DC, Staals RHJ, Jore MM, Brouns SJJ, van der Oost J. 2012. The CRISPRs, they are a-changin’: how prokaryotes generate adaptive immunity. Annu Rev Genet 46:311–339 http://dx.doi.org/10.1146/annurev-genet-110711-155447. [PubMed]
54. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. 2007. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315:1709–1712 http://dx.doi.org/10.1126/science.1138140. [PubMed]
55. Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV. 2006. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol Direct 1:7 http://dx.doi.org/10.1186/1745-6150-1-7. [PubMed]
56. Wiedenheft B, Sternberg SH, Doudna JA. 2012. RNA-guided genetic silencing systems in bacteria and archaea. Nature 482:331–338 http://dx.doi.org/10.1038/nature10886. [PubMed]
57. Grissa I, Vergnaud G, Pourcel C. 2007. The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats. BMC Bioinformatics 8:172 http://dx.doi.org/10.1186/1471-2105-8-172. [PubMed]
58. Makarova KS, Wolf YI, Alkhnbashi OS, Costa F, Shah SA, Saunders SJ, Barrangou R, Brouns SJJ, Charpentier E, Haft DH, Horvath P, Moineau S, Mojica FJM, Terns RM, Terns MP, White MF, Yakunin AF, Garrett RA, van der Oost J, Backofen R, Koonin EV. 2015. An updated evolutionary classification of CRISPR-Cas systems. Nat Rev Microbiol 13:722–736 http://dx.doi.org/10.1038/nrmicro3569. [PubMed]
59. Haft DH, Selengut J, Mongodin EF, Nelson KE. 2005. A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes. PLOS Comput Biol 1:e60 http://dx.doi.org/10.1371/journal.pcbi.0010060. [PubMed]
60. Horvath P, Barrangou R. 2010. CRISPR/Cas, the immune system of bacteria and archaea. Science 327:167–170 http://dx.doi.org/10.1126/science.1179555. [PubMed]
61. Nuñez JK, Lee ASY, Engelman A, Doudna JA. 2015. Integrase-mediated spacer acquisition during CRISPR-Cas adaptive immunity. Nature 519:193–198 http://dx.doi.org/10.1038/nature14237. [PubMed]
62. Marraffini LA. 2015. CRISPR-Cas immunity in prokaryotes. Nature 526:55–61 http://dx.doi.org/10.1038/nature15386. [PubMed]
63. Yosef I, Goren MG, Qimron U. 2012. Proteins and DNA elements essential for the CRISPR adaptation process in Escherichia coli. Nucleic Acids Res 40:5569–5576 http://dx.doi.org/10.1093/nar/gks216. [PubMed]
64. Levy A, Goren MG, Yosef I, Auster O, Manor M, Amitai G, Edgar R, Qimron U, Sorek R. 2015. CRISPR adaptation biases explain preference for acquisition of foreign DNA. Nature 520:505–510 http://dx.doi.org/10.1038/nature14302. [PubMed]
65. Modell JW, Jiang W, Marraffini LA. 2017. CRISPR-Cas systems exploit viral DNA injection to establish and maintain adaptive immunity. Nature 544:101–104 http://dx.doi.org/10.1038/nature21719. [PubMed]
66. Wright AV, Liu J-J, Knott GJ, Doxzen KW, Nogales E, Doudna JA. 2017. Structures of the CRISPR genome integration complex. Science 357:1113–1118 http://dx.doi.org/10.1126/science.aao0679. [PubMed]
67. Jansen R, Embden JD, Gaastra W, Schouls LM. 2002. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 43:1565–1575 http://dx.doi.org/10.1046/j.1365-2958.2002.02839.x. [PubMed]
68. Pougach K, Semenova E, Bogdanova E, Datsenko KA, Djordjevic M, Wanner BL, Severinov K. 2010. Transcription, processing and function of CRISPR cassettes in Escherichia coli. Mol Microbiol 77:1367–1379 http://dx.doi.org/10.1111/j.1365-2958.2010.07265.x. [PubMed]
69. Haurwitz RE, Jinek M, Wiedenheft B, Zhou K, Doudna JA. 2010. Sequence- and structure-specific RNA processing by a CRISPR endonuclease. Science 329:1355–1358 http://dx.doi.org/10.1126/science.1192272. [PubMed]
70. Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, Eckert MR, Vogel J, Charpentier E. 2011. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471:602–607 http://dx.doi.org/10.1038/nature09886. [PubMed]
71. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821 http://dx.doi.org/10.1126/science.1225829. [PubMed]
72. Zhang Q, Ye Y. 2017. Not all predicted CRISPR-Cas systems are equal: isolated cas genes and classes of CRISPR like elements. BMC Bioinformatics 18:92 http://dx.doi.org/10.1186/s12859-017-1512-4. [PubMed]
73. Brouns SJJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJH, Snijders APL, Dickman MJ, Makarova KS, Koonin EV, van der Oost J. 2008. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321:960–964 http://dx.doi.org/10.1126/science.1159689. [PubMed]
74. Strutt SC, Torrez RM, Kaya E, Negrete OA, Doudna JA. 2018. RNA-dependent RNA targeting by CRISPR-Cas9. eLife 7:e32724 http://dx.doi.org/10.7554/eLife.32724. [PubMed]
75. Holt DC, Holden MTG, Tong SYC, Castillo-Ramirez S, Clarke L, Quail MA, Currie BJ, Parkhill J, Bentley SD, Feil EJ, Giffard PM. 2011. A very early-branching Staphylococcus aureus lineage lacking the carotenoid pigment staphyloxanthin. Genome Biol Evol 3:881–895 http://dx.doi.org/10.1093/gbe/evr078. [PubMed]
76. Tong SYC, Schaumburg F, Ellington MJ, Corander J, Pichon B, Leendertz F, Bentley SD, Parkhill J, Holt DC, Peters G, Giffard PM. 2015. Novel staphylococcal species that form part of a Staphylococcus aureus-related complex: the non-pigmented Staphylococcus argenteus sp. nov. and the non-human primate-associated Staphylococcus schweitzeri sp. nov. Int J Syst Evol Microbiol 65:15–22 http://dx.doi.org/10.1099/ijs.0.062752-0. [PubMed]
77. Cramton SE, Schnell NF, Götz F, Brückner R. 2000. Identification of a new repetitive element in Staphylococcus aureus. Infect Immun 68:2344–2348 http://dx.doi.org/10.1128/IAI.68.4.2344-2348.2000. [PubMed]
78. Purves J, Blades M, Arafat Y, Malik SA, Bayliss CD, Morrissey JA. 2012. Variation in the genomic locations and sequence conservation of STAR elements among staphylococcal species provides insight into DNA repeat evolution. BMC Genomics 13:515 http://dx.doi.org/10.1186/1471-2164-13-515. [PubMed]
79. Kinnevey PM, Shore AC, Brennan GI, Sullivan DJ, Ehricht R, Monecke S, Slickers P, Coleman DC. 2013. Emergence of sequence type 779 methicillin-resistant Staphylococcus aureus harboring a novel pseudo staphylococcal cassette chromosome mec (SCC mec)-SCC-SCC CRISPR composite element in Irish hospitals. Antimicrob Agents Chemother 57:524–531 http://dx.doi.org/10.1128/AAC.01689-12. [PubMed]
80. Nishimasu H, Cong L, Yan WX, Ran FA, Zetsche B, Li Y, Kurabayashi A, Ishitani R, Zhang F, Nureki O. 2015. Crystal structure of Staphylococcus aureus Cas9. Cell 162:1113–1126 http://dx.doi.org/10.1016/j.cell.2015.08.007. [PubMed]
81. Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, Koonin EV, Sharp PA, Zhang F. 2015. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520:186–191 http://dx.doi.org/10.1038/nature14299. [PubMed]
82. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F. 2013. Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823 http://dx.doi.org/10.1126/science.1231143. [PubMed]
83. Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J. 2013. RNA-programmed genome editing in human cells. eLife 2:e00471 http://dx.doi.org/10.7554/eLife.00471. [PubMed]
84. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. 2013. RNA-guided human genome engineering via Cas9. Science 339:823–826 http://dx.doi.org/10.1126/science.1232033. [PubMed]
85. Sakuma T, Nishikawa A, Kume S, Chayama K, Yamamoto T. 2015. Multiplex genome engineering in human cells using all-in-one CRISPR/Cas9 vector system. Sci Rep 4:5400. [PubMed]
86. Agari Y, Sakamoto K, Tamakoshi M, Oshima T, Kuramitsu S, Shinkai A. 2010. Transcription profile of Thermus thermophilus CRISPR systems after phage infection. J Mol Biol 395:270–281 http://dx.doi.org/10.1016/j.jmb.2009.10.057. [PubMed]
87. Quax TEF, Voet M, Sismeiro O, Dillies M-A, Jagla B, Coppée J-Y, Sezonov G, Forterre P, van der Oost J, Lavigne R, Prangishvili D. 2013. Massive activation of archaeal defense genes during viral infection. J Virol 87:8419–8428 http://dx.doi.org/10.1128/JVI.01020-13. [PubMed]
88. Young JC, Dill BD, Pan C, Hettich RL, Banfield JF, Shah M, Fremaux C, Horvath P, Barrangou R, Verberkmoes NC. 2012. Phage-induced expression of CRISPR-associated proteins is revealed by shotgun proteomics in Streptococcus thermophilus. PLoS One 7:e38077 http://dx.doi.org/10.1371/journal.pone.0038077. [PubMed]
89. Perez-Rodriguez R, Haitjema C, Huang Q, Nam KH, Bernardis S, Ke A, DeLisa MP. 2011. Envelope stress is a trigger of CRISPR RNA-mediated DNA silencing in Escherichia coli. Mol Microbiol 79:584–599 http://dx.doi.org/10.1111/j.1365-2958.2010.07482.x. [PubMed]
90. Patterson AG, Jackson SA, Taylor C, Evans GB, Salmond GPC, Przybilski R, Staals RHJ, Fineran PC. 2016. Quorum sensing controls adaptive immunity through the regulation of multiple CRISPR-Cas systems. Mol Cell 64:1102–1108 http://dx.doi.org/10.1016/j.molcel.2016.11.012. [PubMed]
91. Høyland-Kroghsbo NM, Paczkowski J, Mukherjee S, Broniewski J, Westra E, Bondy-Denomy J, Bassler BL. 2017. Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system. Proc Natl Acad Sci U S A 114:131–135 http://dx.doi.org/10.1073/pnas.1617415113. [PubMed]
92. Kang YK, Kwon K, Ryu JS, Lee HN, Park C, Chung HJ. 2017. Nonviral genome editing based on a polymer-derivatized CRISPR nanocomplex for targeting bacterial pathogens and antibiotic resistance. Bioconjug Chem 28:957–967 http://dx.doi.org/10.1021/acs.bioconjchem.6b00676. [PubMed]
93. Nitzan M, Fechter P, Peer A, Altuvia Y, Bronesky D, Vandenesch F, Romby P, Biham O, Margalit H. 2015. A defense-offense multi-layered regulatory switch in a pathogenic bacterium. Nucleic Acids Res 43:1357–1369 http://dx.doi.org/10.1093/nar/gkv001. [PubMed]
94. Audretsch C, Lopez D, Srivastava M, Wolz C, Dandekar T. 2013. A semi-quantitative model of quorum-sensing in Staphylococcus aureus, approved by microarray meta-analyses and tested by mutation studies. Mol Biosyst 9:2665–2680 http://dx.doi.org/10.1039/c3mb70117d. [PubMed]
95. Jelsbak L, Hemmingsen L, Donat S, Ohlsen K, Boye K, Westh H, Ingmer H, Frees D. 2010. Growth phase-dependent regulation of the global virulence regulator Rot in clinical isolates of Staphylococcus aureus. Int J Med Microbiol 300:229–236 http://dx.doi.org/10.1016/j.ijmm.2009.07.003. [PubMed]
96. Song J, Lays C, Vandenesch F, Benito Y, Bes M, Chu Y, Lina G, Romby P, Geissmann T, Boisset S. 2012. The expression of small regulatory RNAs in clinical samples reflects the different life styles of Staphylococcus aureus in colonization vs. infection. PLoS One 7:e37294 http://dx.doi.org/10.1371/journal.pone.0037294. [PubMed]
97. Montgomery CP, Boyle-Vavra S, Adem PV, Lee JC, Husain AN, Clasen J, Daum RS. 2008. Comparison of virulence in community-associated methicillin-resistant Staphylococcus aureus pulsotypes USA300 and USA400 in a rat model of pneumonia. J Infect Dis 198:561–570 http://dx.doi.org/10.1086/590157. [PubMed]
98. Montgomery CP, Boyle-Vavra S, Daum RS. 2010. Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection. PLoS One 5:e15177 http://dx.doi.org/10.1371/journal.pone.0015177. [PubMed]
99. Bordeau V, Cady A, Revest M, Rostan O, Sassi M, Tattevin P, Donnio P-Y, Felden B. 2016. Staphylococcus aureus regulatory RNAs as potential biomarkers for bloodstream infections. Emerg Infect Dis 22:1570–1578 http://dx.doi.org/10.3201/eid2209.151801. [PubMed]
100. Painter KL, Krishna A, Wigneshweraraj S, Edwards AM. 2014. What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia? Trends Microbiol 22:676–685 http://dx.doi.org/10.1016/j.tim.2014.09.002. [PubMed]
101. Pollitt EJG, West SA, Crusz SA, Burton-Chellew MN, Diggle SP. 2014. Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus. Infect Immun 82:1045–1051 http://dx.doi.org/10.1128/IAI.01216-13. [PubMed]
102. Chabelskaya S, Gaillot O, Felden B. 2010. A Staphylococcus aureus small RNA is required for bacterial virulence and regulates the expression of an immune-evasion molecule. PLoS Pathog 6:e1000927 http://dx.doi.org/10.1371/journal.ppat.1000927. [PubMed]
103. Pichon C, Felden B. 2005. Small RNA genes expressed from Staphylococcus aureus genomic and pathogenicity islands with specific expression among pathogenic strains. Proc Natl Acad Sci U S A 102:14249–14254 http://dx.doi.org/10.1073/pnas.0503838102. [PubMed]
104. Haupt K, Reuter M, van den Elsen J, Burman J, Hälbich S, Richter J, Skerka C, Zipfel PF. 2008. The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement factor H and C3b. PLoS Pathog 4:e1000250 http://dx.doi.org/10.1371/journal.ppat.1000250. [PubMed]
105. Zhang L, Jacobsson K, Vasi J, Lindberg M, Frykberg L. 1998. A second IgG-binding protein in Staphylococcus aureus. Microbiology 144:985–991 http://dx.doi.org/10.1099/00221287-144-4-985. [PubMed]
106. Anderson KL, Roberts C, Disz T, Vonstein V, Hwang K, Overbeek R, Olson PD, Projan SJ, Dunman PM. 2006. Characterization of the Staphylococcus aureus heat shock, cold shock, stringent, and SOS responses and their effects on log-phase mRNA turnover. J Bacteriol 188:6739–6756 http://dx.doi.org/10.1128/JB.00609-06. [PubMed]
107. Morrison JM, Miller EW, Benson MA, Alonzo F III, Yoong P, Torres VJ, Hinrichs SH, Dunman PM. 2012. Characterization of SSR42, a novel virulence factor regulatory RNA that contributes to the pathogenesis of a Staphylococcus aureus USA300 representative. J Bacteriol 194:2924–2938 http://dx.doi.org/10.1128/JB.06708-11. [PubMed]
108. Das S, Lindemann C, Young BC, Muller J, Österreich B, Ternette N, Winkler A-C, Paprotka K, Reinhardt R, Förstner KU, Allen E, Flaxman A, Yamaguchi Y, Rollier CS, van Diemen P, Blättner S, Remmele CW, Selle M, Dittrich M, Müller T, Vogel J, Ohlsen K, Crook DW, Massey R, Wilson DJ, Rudel T, Wyllie DH, Fraunholz MJ. 2016. Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation. Proc Natl Acad Sci U S A 113:E3101–E3110 http://dx.doi.org/10.1073/pnas.1520255113. [PubMed]
109. Kaito C, Saito Y, Ikuo M, Omae Y, Mao H, Nagano G, Fujiyuki T, Numata S, Han X, Obata K, Hasegawa S, Yamaguchi H, Inokuchi K, Ito T, Hiramatsu K, Sekimizu K. 2013. Mobile genetic element SCCmec-encoded psm-mec RNA suppresses translation of agrA and attenuates MRSA virulence. PLoS Pathog 9:e1003269 http://dx.doi.org/10.1371/journal.ppat.1003269. [PubMed]
110. Qin L, McCausland JW, Cheung GYC, Otto M. 2016. PSM-Mec-A virulence determinant that connects transcriptional regulation, virulence, and antibiotic resistance in staphylococci. Front Microbiol 7:1293 http://dx.doi.org/10.3389/fmicb.2016.01293. [PubMed]
111. Kaito C, Saito Y, Nagano G, Ikuo M, Omae Y, Hanada Y, Han X, Kuwahara-Arai K, Hishinuma T, Baba T, Ito T, Hiramatsu K, Sekimizu K. 2011. Transcription and translation products of the cytolysin gene psm-mec on the mobile genetic element SCC mec regulate Staphylococcus aureus virulence. PLoS Pathog 7:e1001267 http://dx.doi.org/10.1371/journal.ppat.1001267. [PubMed]
112. Crosby HA, Schlievert PM, Merriman JA, King JM, Salgado-Pabón W, Horswill AR. 2016. The Staphylococcus aureus global regulator MgrA modulates clumping and virulence by controlling surface protein expression. PLoS Pathog 12:e1005604 http://dx.doi.org/10.1371/journal.ppat.1005604. [PubMed]
113. Krismer B, Weidenmaier C, Zipperer A, Peschel A. 2017. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat Rev Microbiol 15:675–687 http://dx.doi.org/10.1038/nrmicro.2017.104. [PubMed]
114. Brown AF, Leech JM, Rogers TR, McLoughlin RM. 2014. Staphylococcus aureus colonization: modulation of host immune response and impact on human vaccine design. Front Immunol 4:507 http://dx.doi.org/10.3389/fimmu.2013.00507.
115. Pynnonen M, Stephenson RE, Schwartz K, Hernandez M, Boles BR. 2011. Hemoglobin promotes Staphylococcus aureus nasal colonization. PLoS Pathog 7:e1002104 http://dx.doi.org/10.1371/journal.ppat.1002104. [PubMed]
116. Ramsey MM, Freire MO, Gabrilska RA, Rumbaugh KP, Lemon KP. 2016. Staphylococcus aureus shifts toward commensalism in response to Corynebacterium species. Front Microbiol 7:1230 http://dx.doi.org/10.3389/fmicb.2016.01230. [PubMed]
117. Hermansen GMM, Sazinas P, Kofod D, Millard A, Andersen PS, Jelsbak L. 2018. Transcriptomic profiling of interacting nasal staphylococci species reveals global changes in gene and non-coding RNA expression. FEMS Microbiol Lett 365: http://dx.doi.org/10.1093/femsle/fny004.

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Regulatory RNAs, present in many bacterial genomes and particularly in pathogenic bacteria such as , control the expression of genes encoding virulence factors or metabolic proteins. They are extremely diverse and include noncoding RNAs (sRNA), antisense RNAs, and some 5′ or 3′ untranslated regions of messenger RNAs that act as sensors for metabolites, tRNAs, or environmental conditions (e.g., temperature, pH). In this review we focus on specific examples of sRNAs of that illustrate how numerous sRNAs and associated proteins are embedded in complex networks of regulation. In addition, we discuss the CRISPR-Cas systems defined as an RNA-interference-like mechanism, which also exist in staphylococcal strains.

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Image of FIGURE 1

Several mechanisms of RNA regulation in . Schematic drawing of the flavin mononucleotide riboswitch. The 5′ UTR adopts a particular structure recognized by the flavin mononucleotide, which in turn leads to the stabilization of a stem-loop structure sequestrating the SD sequence to inhibit translation. 30S is for the small ribosomal subunit. An example of a T-box motif as found in the 5′ UTR of many mRNAs encoding aminoacyl-tRNA synthetases. Nonaminoacylated tRNA binds to the leader region at two sites and stabilizes an antiterminator structure, allowing transcription of the downstream gene. The drawing is adapted from reference 4. The 3′ UTR of the biofilm repressor IcaR possesses a cytosine-rich motif, which binds to the SD sequence and hinders ribosomes from its binding site on the mRNA (see text for details). Overlapping 5′ UTRs of G and H mRNAs are processed by the endoribonuclease III (Rnase III). Shorter 5′ ends might facilitate ribosome recruitment. The antitoxin RNA SprF1 interacts at the 3′ end of the toxin encoded by sprG1 and triggers its degradation. A cluster of five sRNAs was sequenced in the Newman strain that encodes a putative toxin-antitoxin system (see text for details). sRNAs act by an antisense mechanism. Binding of the 5′ UTR of RNAIII to the 5′ UTR of mRNA liberates its SD and activated translation (g), whereas the 3′ domain of RNAIII acts as a repressor domain, which contains C-rich motifs for base-pairing with the SD sequence of mRNA as mRNA depicted in the figure (h). Green bar, SD sequence; black circle, RNase III (for references and more details, see text).

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0038-2018
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Image of FIGURE 2

Examples of the complex network between sRNAs and transcriptional factors in in response to stress. Arrows show activation and bars show repression. Blue, transcriptional regulators; green, two-component systems; red, regulatory sRNAs. Red lines corresponded to posttranscriptional regulation, and black lines, to transcriptional regulation. Dotted lines are for the target mRNAs that were not experimentally validated. Only sRNA-dependent mRNA targets encoding transcriptional factors are depicted in the figure.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0038-2018
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Image of FIGURE 3

Genomic organization of the loci for the type III-A CRISPR system of strain 08BA02176. Type III is the typical CRISPR organization. The scheme was obtained using CRISPRone ( 72 ), and the genome sequence was deposited in GenBank (accession number 08BA02176; RefSeq accession number GCF_000296595.1). Genomic organization of the loci for the type II-C CRISPR system of strain M06/0171. The CRISPR-Cas genes were found on an SCC inserted into the 3′ end of the chromosomally located gene. The scheme was obtained using CRISPRone ( 72 ), and the SCCmec sequence was deposited in GenBank (GenBank accession number HE980450.1). Cartoon (RNA and DNA) and surface (Cas9) representations of the SaCas9-sgRNA-target DNA complex (pdb file 5AXW) ( 80 ). The SaCas9 sgRNA consists of the crRNA guide region (crGUIDE represented in pale yellow) forming a heteroduplex with the target DNA strand (tDNA in magenta) and the repeat/antirepeat helix (blue, the repeat crRNA-derived strand, green, the antirepeat trascrRNA-derived strand). The protospacer adjacent region-containing DNA duplex is red. Cas9 domains are colored as follows: cyan, WED domain; pale orange, REC domain; gray, NUC domain. Molecular graphics images were prepared using PyMol.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0038-2018
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