Bacterial small RNA

From Wikipedia, the free encyclopedia
Jump to: navigation, search

Bacterial small RNAs (sRNA) are small (50-250 nucleotide) non-coding RNA molecules produced by bacteria; they are highly structured and contain several stem-loops.[1][2] Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alpha-proteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis (the causative agent of tularaemia) and the plant pathogen Xanthomonas oryzae pathovar oryzae.[3][4][5][6][7][8][9][10][11]

In the 1960s, the abbreviation sRNA was used to refer to "soluble RNA," which is now known as transfer RNA or tRNA (for an example of the abbreviation used in this sense, see.[12])


Most bacterial sRNAs are encoded by free-standing genes located in the intergenic regions (IGR) between two known genes.[5][6] However, a class of sRNAs are shown to be derived from the 3'-UTR of mRNAs by independent transcription or nucleolytic cleavage.[13]


sRNAs can either bind to protein targets, and modify the function of the bound protein, or bind to mRNA targets and regulate gene expression. Antisense sRNAs can be categorised as cis-encoded sRNAs, where there is an overlap between the antisense sRNA and the target gene, and trans-encoded sRNAs, where the antisense sRNA gene is separate from the target gene.[1][14]


Amongst the targets of sRNAs are a number of house-keeping genes. The 6S RNA binds to RNA polymerase and regulates transcription, tmRNA has functions in protein synthesis, including the recycling of stalled ribosomes, 4.5S RNA regulates signal recognition particle (SRP), which is required for the secretion of proteins and RNase P is involved in maturing tRNAs.[15][16]

Stress response[edit]

Many sRNAs are involved in stress response regulation.[17] They are expressed under stress conditions such as cold shock, iron depletion, onset of the SOS response and sugar stress.[16] The small RNA nitrogen stress-induced RNA 1 (NsiR1) is produced by Cyanobacteria under conditions of nitrogen deprivation.[18]

Regulation of RpoS[edit]

The RpoS gene in E. coli encodes sigma 38, a sigma factor which regulates stress response and acts as a transcriptional regulator for many genes involved in cell adaptation. At least three sRNAs, DsrA, RprA and OxyS, regulate the translation of RpoS. DsrA and RprA both activate RpoS translation by base pairing to a region in the leader sequence of the RpoS mRNA and disrupting formation of a hairpin which frees up the ribosome loading site. OxyS inhibits RpoS translation. DsrA levels are increased in response to low temperatures and osmotic stress, and RprA levels are increased in response to osmotic stress and cell-surface stress, therefore increasing RpoS levels in response to these conditions. Levels of OxyS are increased in response to oxidative stress, therefore inhibiting RpoS under these conditions.[16][19][20]

Regulation of outer membrane proteins[edit]

The outer membrane of gram negative bacteria acts as a barrier to prevent the entry of toxins into the bacterial cell, and plays a role in the survival of bacterial cells in diverse environments. Outer membrane proteins (OMPs) include porins and adhesins. Numerous sRNAs regulate the expression of OMPs. The porins OmpC and OmpF are responsible for the transport of metabolites and toxins. The expression of OmpC and OmpF is regulated by the sRNAs MicC and MicF in response to stress conditions.[21][22][23] The outer membrane protein OmpA anchors the outer membrane to the murein layer of the periplasmic space. Its expression is downregulated in the stationary phase of cell-growth. In E. coli the sRNA MicA depletes OmpA levels, in Vibrio cholerae the sRNA VrrA represses synthesis of OmpA in response to stress.[21][24]


In some bacteria sRNAs regulate virulence genes. In Salmonella, the pathogenicity island encoded InvR RNA represses synthesis of the major outer membrane protein OmpD; another co-activated DapZ sRNA from 3'-UTR represses abundant membrane Opp/Dpp transporters of oligopeptides;[13] and SgrS sRNA regulates the expression of the secreted effector protein SopD.[4] In Staphylococcus aureus, RNAIII regulates a number of genes involved in toxin and enzyme production and cell-surface proteins.[16] The FasX and Pel sRNAs in Streptococcus pyogenes are encoded in loci associated with virulence. Pel RNA activates synthesis of surface-associated and secreted proteins.[16]

Quorum sensing[edit]

In Vibrio species, the Qrr sRNAs and the chaperone protein Hfq are involved in the regulation of quorum sensing. Qrr sRNAs regulate the expression of several mRNAs including the quorum-sensing master regulators LuxR and HapR.[25][26]

Target prediction[edit]

In order to understand an sRNA's function one primarily needs to describe its targets. Here, target predictions represent a sensible, fast and free method for initial characterization of putative targets, given that the sRNA actually exerts its function via direct base pairing with a target RNA. Examples are CopraRNA,[27][28] IntaRNA,[28][29] TargetRNA[30] and RNApredator.[31]


BSRD ( is a repository for published sRNA sequences with multiple valuable annotations and expression profiles.[32]

See also[edit]


  1. ^ a b Vogel J, Wagner EG (June 2007). "Target identification of small noncoding RNAs in bacteria". Curr. Opin. Microbiol. 10 (3): 262–70. doi:10.1016/j.mib.2007.06.001. PMID 17574901. 
  2. ^ Viegas SC, Arraiano CM (2008). "Regulating the regulators: How ribonucleases dictate the rules in the control of small non-coding RNAs". RNA Biol 5 (4): 230–43. doi:10.4161/rna.6915. PMID 18981732. 
  3. ^ Hershberg R, Altuvia S, Margalit H (April 2003). "A survey of small RNA-encoding genes in Escherichia coli". Nucleic Acids Res. 31 (7): 1813–20. doi:10.1093/nar/gkg297. PMC 152812. PMID 12654996. 
  4. ^ a b Vogel J (January 2009). "A rough guide to the non-coding RNA world of Salmonella". Mol. Microbiol. 71 (1): 1–11. doi:10.1111/j.1365-2958.2008.06505.x. PMID 19007416. 
  5. ^ a b Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S (July 2001). "Identification of novel small RNAs using comparative genomics and microarrays". Genes Dev. 15 (13): 1637–51. doi:10.1101/gad.901001. PMC 312727. PMID 11445539. 
  6. ^ a b Argaman L, Hershberg R, Vogel J; et al. (June 2001). "Novel small RNA-encoding genes in the intergenic regions of Escherichia coli". Curr. Biol. 11 (12): 941–50. doi:10.1016/S0960-9822(01)00270-6. PMID 11448770. 
  7. ^ Rivas E, Klein RJ, Jones TA, Eddy SR (September 2001). "Computational identification of noncoding RNAs in E. coli by comparative genomics". Curr. Biol. 11 (17): 1369–73. doi:10.1016/S0960-9822(01)00401-8. PMID 11553332. 
  8. ^ Schlüter JP, Reinkensmeier J, Daschkey S; et al. (2010). "A genome-wide survey of sRNAs in the symbiotic nitrogen-fixing alpha-proteobacterium Sinorhizobium meliloti". BMC Genomics 11: 245. doi:10.1186/1471-2164-11-245. PMC 2873474. PMID 20398411. 
  9. ^ Axmann IM, Kensche P, Vogel J, Kohl S, Herzel H, Hess WR (2005). "Identification of cyanobacterial non-coding RNAs by comparative genome analysis". Genome Biol. 6 (9): R73. doi:10.1186/gb-2005-6-9-r73. PMC 1242208. PMID 16168080. 
  10. ^ Postic G, Frapy E, Dupuis M; et al. (2010). "Identification of small RNAs in Francisella tularensis". BMC Genomics 11: 625. doi:10.1186/1471-2164-11-625. PMC 3091763. PMID 21067590. 
  11. ^ Liang H, Zhao YT, Zhang JQ, Wang XJ, Fang RX, Jia YT (2011). "Identification and functional characterization of small non-coding RNAs in Xanthomonas oryzae pathovar oryzae". BMC Genomics 12: 87. doi:10.1186/1471-2164-12-87. PMC 3039613. PMID 21276262. 
  12. ^ Crick F (1966). "Codon–anticodon pairing: the wobble hypothesis" (PDF). J Mol Biol 19 (2): 548–55. doi:10.1016/S0022-2836(66)80022-0. PMID 5969078. 
  13. ^ a b Chao Y, Papenfort K, Reinhardt R, Sharma CM, Vogel J. (October 2012). "An atlas of Hfq-bound transcripts reveals 3' UTRs as a genomic reservoir of regulatory small RNAs.". EMBO J. 31 (20): 4005–19. doi:10.1038/emboj.2012.229. PMID 22922465. 
  14. ^ Cao Y, Wu J, Liu Q; et al. (November 2010). "sRNATarBase: a comprehensive database of bacterial sRNA targets verified by experiments". RNA 16 (11): 2051–7. doi:10.1261/rna.2193110. PMC 2957045. PMID 20843985. 
  15. ^ Wassarman KM (April 2007). "6S RNA: a small RNA regulator of transcription". Curr. Opin. Microbiol. 10 (2): 164–8. doi:10.1016/j.mib.2007.03.008. PMID 17383220. 
  16. ^ a b c d e Christian Hammann; Nellen, Wolfgang (2005). Small RNAs:: Analysis and Regulatory Functions (Nucleic Acids and Molecular Biology). Berlin: Springer. ISBN 3-540-28129-0. 
  17. ^ Caswell CC, Oglesby-Sherrouse AG, Murphy ER (October 2014). "Sibling rivalry: related bacterial small RNAs and their redundant and non-redundant roles". Front Cell Infect Microbiol 2014 (4): 151. doi:10.3389/fcimb.2014.00151. PMC 4211561. PMID 25389522. 
  18. ^ Ionescu, D; Voss, B; Oren, A; Hess, WR; Muro-Pastor, AM (Apr 30, 2010). "Heterocyst-specific transcription of NsiR1, a non-coding RNA encoded in a tandem array of direct repeats in cyanobacteria.". Journal of Molecular Biology 398 (2): 177–88. doi:10.1016/j.jmb.2010.03.010. PMID 20227418. 
  19. ^ Repoila F, Majdalani N, Gottesman S (May 2003). "Small non-coding RNAs, co-ordinators of adaptation processes in Escherichia coli: the RpoS paradigm". Mol. Microbiol. 48 (4): 855–61. doi:10.1046/j.1365-2958.2003.03454.x. PMID 12753181. 
  20. ^ Benjamin JA, Desnoyers G, Morissette A, Salvail H, Massé E (March 2010). "Dealing with oxidative stress and iron starvation in microorganisms: an overview". Can. J. Physiol. Pharmacol. 88 (3): 264–72. doi:10.1139/y10-014. PMID 20393591. 
  21. ^ a b Vogel J, Papenfort K (December 2006). "Small non-coding RNAs and the bacterial outer membrane". Curr. Opin. Microbiol. 9 (6): 605–11. doi:10.1016/j.mib.2006.10.006. PMID 17055775. 
  22. ^ Delihas N, Forst S (October 2001). "MicF: an antisense RNA gene involved in response of Escherichia coli to global stress factors". J. Mol. Biol. 313 (1): 1–12. doi:10.1006/jmbi.2001.5029. PMID 11601842. 
  23. ^ Chen S, Zhang A, Blyn LB, Storz G (October 2004). "MicC, a second small-RNA regulator of Omp protein expression in Escherichia coli". J. Bacteriol. 186 (20): 6689–97. doi:10.1128/JB.186.20.6689-6697.2004. PMC 522180. PMID 15466019. 
  24. ^ Song T, Wai SN (July 2009). "A novel sRNA that modulates virulence and environmental fitness of Vibrio cholerae". RNA Biol 6 (3): 254–8. doi:10.4161/rna.6.3.8371. PMID 19411843. 
  25. ^ Lenz DH, Mok KC, Lilley BN, Kulkarni RV, Wingreen NS, Bassler BL (July 2004). "The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae". Cell 118 (1): 69–82. doi:10.1016/j.cell.2004.06.009. PMID 15242645. 
  26. ^ Bardill JP, Zhao X, Hammer BK (April 2011). "The Vibrio cholerae quorum sensing response is mediated by Hfq-dependent sRNA/mRNA base-pairing interactions". Mol Microbiol 80 (5): 1381–94. doi:10.1111/j.1365-2958.2011.07655.x. PMID 21453446. 
  27. ^ Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, Hess WR, Backofen R, Georg J (2013). "Comparative genomics boosts target prediction for bacterial small RNAs.". Proc Natl Acad Sci U S A 110 (37): E3487–E3496. doi:10.1073/pnas.1303248110. PMID 23980183. 
  28. ^ a b Wright PR, Georg J, Mann M, Sorescu DA, Richter AS, Lott S, Kleinkauf R, Hess WR, Backofen R (2014). "CopraRNA and IntaRNA: predicting small RNA targets, networks and interaction domains.". Nucleic Acids Res 42 (Web Server): W119–23. doi:10.1093/nar/gku359. PMID 24838564. 
  29. ^ Busch A, Richter AS, Backofen R (2008). "IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions.". Bioinformatics 24 (24): 2849–56. doi:10.1093/bioinformatics/btn544. PMC 2639303. PMID 18940824. 
  30. ^ Tjaden B, Goodwin SS, Opdyke JA; et al. (2006). "Target prediction for small, noncoding RNAs in bacteria". Nucleic Acids Res. 34 (9): 2791–802. doi:10.1093/nar/gkl356. PMC 1464411. PMID 16717284. 
  31. ^ Eggenhofer F, Tafer H, Stadler PF, Hofacker IL (2011). "RNApredator: fast accessibility-based prediction of sRNA targets". Nucleic Acids Res 39 (Web Server): W149–54. doi:10.1093/nar/gkr467. PMC 3125805. PMID 21672960. 
  32. ^ Li, L; Kwan, HS (January 2013). "BSRD: a repository for bacterial small regulatory RNA.". Nucleic Acids Research 41 (Database issue): D233–8. doi:10.1093/nar/gks1264. PMID 23203879.