Small Regulatory RNAs in Bacteria

Intergenic regions of bacteria contain small regulatory ribonucleic acid (srRNA) genes whose transcripts control expression of distal genes. These transcripts, referred to here as srRNAs, primarily act at the level of translation where they bind messenger RNAs (mRNAs). srRNAs can inhibit or activate a target mRNA. Base pairing with mRNAs is imperfect and includes looped out and/or bulged nucleotide positions and noncanonical base pairs as well. The RNA chaparone protein Hfq is involved in many RNA/RNA interactions and ribonucleases, RNase E and RNase III, have been implicated in the destabilization of several target mRNAs. Gene transcription can also be controlled by an srRNA via binding to the RNA polymerase–sigma factor complex and blocking a functional site on the enzyme complex. Many srRNA genes are transcriptionally activated by environmental stress factors and have complex promoter and upstream regulatory sites involved in this activation. The control of outer membrane protein synthesis in response to stress is one major function of bacterial srRNAs.

Key Concepts

Properties of small regulatory RNA genes; control of gene expression at the level of translation and transcription by RNA; RNA/RNA interactions; imperfect RNA base pairing and noncanonical base pairs; bacterial cell response to environmental stress conditions; mechanisms of mRNA translational inactivation and degradation; macromolecular responses and phenotypic changes in a cell.

Keywords: small regulatory RNA; gene regulation; RNA/RNA interactions; translation; transcription

Figure 1. Generalized representation of an srRNA transcript interacting with a target mRNA. Hfq is the RNA-binding protein that facilitates the RNA/RNA interaction. RBS is the ribosome-binding site on the mRNA. Translation is blocked and in many cases the mRNA is degraded.
Figure 2. Representation of the activation of translation of an mRNA by srRNA. The RBS is normally sequestered in the base pairing of the 5¢ UTR stem loop. When the srRNA is transcribed, it can bind to the 5¢ end of the mRNA and produce a conformational change resulting in the exposure of the RBS.
Figure 3. Interaction of the E. coli micF RNA with the target ompF mRNA. The RNA/RNA duplex structure was determined experimentally. RBS refers to the ribosome-binding site on the mRNA and AUG is the translation start codon. Regulatory and target RNAs from related species of bacteria form similar duplex structures. Modified from Delihas et al. (1997).
Figure 4. Diagrammatic representation of the regulation of ompA RNA by micA RNA. Modified from Udekwu et al. (2005). Left: micA RNA competes for binding to the RBS of ompA mRNA. Hfq facilitates RNA/RNA binding. Right: Model of translation from ompA mRNA (top) and inhibition and initiation of ompA mRNA degradation (bottom). ‘E’ represents RNase E cleavage sites. Reproduced by permission of Cold Spring Harbor Press.
Figure 5. (a) Diagramatic representation of rpoS mRNA showing the RBS sequestered by base pairing that is shown in sections I, II and III. Normal RNase III cleavage sites are also shown. (b) The binding of DsrA RNA to the upstream sequence of rpoS mRNA exposes the RBS (positions –8 to –12) and creates new RNase III cleavage sites. Modified from Resch et al. (2008). Reproduced by permission of the RNA Society.
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 References
    Andersen J and Delihas N (1990) micF RNA binds to the 5¢ end of ompF mRNA and to a protein from E. coli. Biochemistry 29: 9249–9256.
    Andersen J, Delihas N, Ikenaka K et al. (1987) The isolation and characterization of RNA coded by the micF gene in Escherichia coli. Nucleic Acids Research 15: 2089–2101.
    Andersen J, Forst SA, Zhao K, Inouye M and Delihas N (1989) The function of micF RNA. micF RNA is a major factor in the thermal regulation of OmpF protein in E. coli. Journal of Biological Chemistry 264: 17961–17970.
    Antal M, Bordeau V, Douchin V and Felden B (2005) A small bacterial RNA regulates a putative ABC transporter. Journal of Biological Chemistry 280: 7901–7908.
    Babitzke P and Romeo T (2007) CsrB sRNA family: sequestration of RNA-binding regulatory proteins. Current Opinion in Microbiology 10: 156–163.
    Balaban N and Novick RP (1995) Translation of RNAIII, the Staphylococcus aureus agr regulatory RNA molecule, can be activated by a 3¢-end deletion. FEMS Microbiological Letters 133: 155–161.
    Barrandon C, Spiluttini B and Bensaude O (2008) Non-coding RNAs regulating the transcriptional machinery. Biology of the Cell 100: 83–95.
    Boisset S, Geissmann T, Huntzinger E et al. (2007) Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism. Genes & Development 21: 1353–1366.
    Brownlee GG (1971) Sequence of 6S RNA of E. coli. Nature: New Biology 229: 147–149.
    Cavanagh AT, Klocko AD, Liu X and Wassarman KM (2008) Promoter specificity for 6S RNA regulation of transcription is determined by core promoter sequences and competition for region 4.2 of sigma70. Molecular Microbiology 67: 1242–1256.
    Chen S, Zhang A, Blyn LB and Storz G (2004) MicC, a second small-RNA regulator of Omp protein expression in E. coli. Journal of Bacteriology 186: 6689–6697.
    Coyer J, Andersen J, Forst SA, Inouye M and Delihas N (1990) micF RNA in ompB mutants of E. coli: different pathways regulate micF RNA levels in response to osmolarity and temperature change. Journal of Bacteriology 172: 4143–4150.
    Delihas N (2008) Small mobile sequences in bacteria display diverse structure/function motifs. Molecular Microbiology 67: 475–481.
    Delihas N and Forst S (2001) micF: an antisense RNA gene involved in response of E. coli to global stress factors. Journal of Molecular Biology 313: 1–12.
    Delihas N, Rokita SE and Zheng P (1997) Natural antisense RNA/target RNA interactions: possible models for antisense oligonucleotide drug design. Nature Biotechnology 15: 751–753.
    Dupont M, James CE, Chevalier J and Pagès JM (2007) An early response to environmental stress involves regulation of OmpX and OmpF, two enterobacterial outer membrane pore-forming proteins. Antimicrobial Agents and Chemotherapy 51: 3190–3198.
    Griffiths-Jones S, Moxon S, Marshall M et al. (2005) Rfam: annotating non-coding RNAs in complete genomes. Nucleic Acids Research 33(Database issue): D121–D124.
    Guillier M and Gottesman S (2006) Remodelling of the E. coli outer membrane by two small regulatory RNAs. Molecular Microbiology 59: 231–247.
    Hall MN and Silhavy TJ (1981) Genetic analysis of the major outer membrane proteins of E. coli. Annual Review of Genetics 15: 91–142.
    Hindley J (1967) Fractionation of 32P-labeled ribonucleic acids on polyacrylamide gels and their characterization by fingerprinting. Journal of Molecular Biology 30: 125–136.
    Huntzinger E, Boisset S, Saveanu C et al. (2005) Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression. EMBO Journal 24: 824–835.
    Kawano M, Reynolds AA, Miranda-Rios J and Storz G (2005) Detection of 5¢- and 3¢-UTR-derived small RNAs and cis-encoded antisense RNAs in E. coli. Nucleic Acids Research 33: 1040–1050.
    Lease RA and Belfort M (2000) Riboregulation by DsrA RNA: trans-actions for global economy. Molecular Microbiology 38: 667–672.
    Lease RA, Smith D, McDonough K and Belfort M (2004) The small noncoding DsrA RNA is an acid resistance regulator in E. coli. Journal of Bacteriology 186: 6179–6185.
    Liu MY, Gui G, Wei B et al. (1997) The RNA molecule CsrB binds to the global regulatory protein CsrA and antagonizes its activity in E. coli. Journal of Biological Chemistry 272: 17502–17510.
    Mizuno T, Chou MY and Inouye M (1984) A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proceedings of the National Academy of Sciences of the USA 81: 1966–1970.
    Morita T and Aiba H (2007) Small RNAs making a small protein. Proceedings of the National Academy of Sciences of the USA 104: 20149–20150.
    Nilsson G, Belasco JG, Cohen SN and von Gabain A (1984) Growth-rate dependent regulation of mRNA stability in E. coli. Nature 312: 75–77.
    Papamichail D and Delihas N (2006) Outer membrane protein genes and their small noncoding RNA regulator genes in Photorhabdus luminescens. Biology Direct 1: 12.
    Papenfort K, Pfeiffer V, Lucchini S et al. (2008) Systematic deletion of Salmonella small RNA genes identifies CyaR, a conserved CRP-dependent riboregulator of OmpX synthesis. Molecular Microbiology 68: 890–906.
    Resch A, Afonyushkin T, Lombo TB et al. (2008) Translational activation by the noncoding RNA DsrA involves alternative RNase III processing in the rpoS 5¢-leader. RNA 14: 454–459.
    Saetrom P, Sneve R, Kristiansen KI et al. (2005) Predicting non-coding RNA genes in E. coli with boosted genetic programming. Nucleic Acids Research 33: 3263–3270.
    Schmidt M, Zheng P and Delihas N (1995) Secondary structures of E. coli antisense micF RNA, the 5¢-end of the target ompF mRNA, and the RNA/RNA duplex. Biochemistry 34: 3621–3631.
    Sittka A, Lucchini S, Papenfort K et al. (2008) Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator, Hfq. PLoS Genetics 4: e1000163.
    Stoorvogel J, van Bussel MJ and van de Klundert JA (1991) Molecular characterization of an Enterobacter cloacae outer membrane protein (OmpX). Journal of Bacteriology 173: 156–160.
    Storz G, Altuvia S and Wassarman KM (2005) An abundance of RNA regulators. Annual Review of Biochemistry 74: 199–217.
    Tjaden B, Saxena RM, Stolyar S et al. (2002) Transcriptome analysis of E. coli using high-density oligonucleotide probe arrays. Nucleic Acids Research 30: 3732–3738.
    Tomizawa J, Itoh T, Selzer G and Som T (1981) Inhibition of ColE1 RNA primer formation by a plasmid-specified small RNA. Proceedings of the National Academy of Sciences of the USA 78: 1421–1425.
    Udekwu KI, Darfeuille F, Vogel J et al. (2005) Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA. Genes & Development 19: 2355–2366.
    Urban JH and Vogel J (2007) Translational control and target recognition by E. coli small RNAs in vivo. Nucleic Acids Research 35: 1018–1037.
    Vogel J and Papenfort K (2006) Small noncoding RNAs and the bacterial outer membrane. Current Opinion in Microbiology 9: 605–611.
    Wadler CS and Vanderpool CK (2007) A dual function for a bacterial small RNA: sgrS performs base pairing-dependent regulation and encodes a functional polypeptide. Proceedings of the National Academy of Sciences of the USA 104: 20454–20459.
    Wassarman KM (2007) 6S RNA: a regulator of transcription. Molecular Microbiology 65: 1425–1431.
    Wassarman KM and Storz G (2000) 6S RNA regulates E. coli RNA polymerase activity. Cell 101: 613–623.
    Zhang A, Wassarman KM, Rosenow C et al. (2003) Global analysis of small RNA and mRNA targets of Hfq. Molecular Microbiology 50: 1111–1124.
 Further Reading
    Fozo EM, Kawano M, Fontaine F et al. (2008) Repression of small toxic protein synthesis by the Sib and OhsC small RNAs. Molecular Microbiology 70: 1076–1093.
    Görke B and Vogel J (2008) Noncoding RNA control of the making and breaking of sugars. Genes & Development 22: 2914–2925.
    Mercer TR, Dinger ME, Mariani J et al. (2008) Noncoding RNAs in long-term memory formation. Neuroscientist 14: 434–445.
    Sittka A and Vogel J (2008) A glimpse at the evolution of virulence control. Cell Host & Microbe 4: 310–312.
    Storz G, Opdyke JA and Wassarman KM (2006) Regulating bacterial transcription with small RNAs. Cold Spring Harbor Symposia on Quantitative Biology 71: 269–273.
    Viegas SC and Arraiano CM (2008) Regulating the regulators: how ribonucleases dictate the rules in the control of small non-coding RNAs. RNA Biology 5: 22–35.
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Delihas, Nicholas(Mar 2009) Small Regulatory RNAs in Bacteria. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000970.pub2]