Small Regulatory RNAs in Bacteria


Intergenic regions of bacteria contain small regulatory ribonucleic acid (sRNA) genes whose transcripts control expression of distal genes. These transcripts, referred to as sRNAs, primarily act at the level of translation where they bind messenger ribonucleic acids (mRNAs) and inhibit or activate a target mRNA. Base pairing with mRNAs is generally imperfect and can include noncanonical base pairs. The RNA chaperone protein Hfq is involved in many RNA/RNA interactions and ribonucleases RNase E and RNase III have been implicated in destabilisation of target mRNAs. Many sRNAs can inhibit multiple mRNAs; however, some sRNAs bind proteins and can regulate transcription or translation indirectly. Some act like ‘sponges’ that bind and sequester proteins involved in global gene regulation. Many sRNA genes are activated by environmental stress factors, and the sRNA genes have complex upstream regulatory sites. Further insight into broad functions of sRNAs comes from human host cells infected by pathogenic bacteria, which reveals a role of sRNA in both virulence and response in human host cell molecular functions, for example changes in long noncoding RNAs and microRNAs. Bacterial regulatory RNAs are proving to be remarkable factors in both cell physiology and bacterial pathogenesis and these RNAs have opened a new world in molecular biology.

Key Concepts

  • Small regulatory RNA genes have been found in most bacterial species. sRNA transcripts are generally less than 200 nt.
  • sRNAs can control gene expression at the level of translation or transcription.
  • sRNAs respond to environmental or internal stress conditions.
  • sRNAs generally form small and imperfect RNA/RNA base pairing with target mRNA; noncanonical base pairs can also be present.
  • sRNAs can inhibit translational and/or induce degradation of target mRNA.
  • Many sRNAs regulate multiple target mRNAs.
  • sRNAs can indirectly regulate the expression of global genes, some by binding proteins that control gene expression.
  • sRNAs can play a major role in bacterial pathogenicity and influence eukaryotic host molecular functions such as levels of host cell microRNA and long noncoding RNA.

Keywords: small regulatory RNAs; control of gene regulation; RNA/RNA interactions; translational or transcriptional inhibition by sRNAs; sRNAs and pathogenicity

Figure 1. Generalised representation of an sRNA (small regulatory ribonucleic acid) transcript interacting with a target mRNA (regulatory ribonucleic acid messenger). The binding interactions are small in length, involving less than ∼20 bp and contain imperfect pairings. 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. sRNAs can also bind to the coding region of the target mRNA and induce cleavage by RNase E (Pfeiffer et al., ).
Figure 2. Representation of the activation of translation of an mRNA by sRNA. The RBS is normally sequestered in the base pairing of the 5′ UTR stem loop. When the sRNA 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 by structure probing (Schmidt et al., ); however, the long range base pairing shown between the 5′‐end bases of MicF RNA and bases 46–50 of ompF mRNA was predicted computationally from the Maximum Weighted Matching program (Tabaska et al., ). RBS refers to the RBS on the mRNA and AUG is the translation start codon. Regulatory and target RNAs from related species of bacteria form similar duplex structures. Reproduced with permission from Delihas and Forst © Elsevier.
Figure 4. ‘Circular’ regulation: posttranscriptional regulation of lrp mRNA by MicF RNA in nutrient‐rich growth media and transcriptional regulation of micF by Lrp in nutrient‐poor media (after Holmqvist et al., ). Lower left of the figure: multiple mRNAs that can be inhibited by MicF RNA under varying conditions (after Corcoran et al., ). MicF RNA binds upstream in the 5′ UTR of yahO mRNA (green), disrupts a protective stem loop structure and induces degradation of the message. Reproduced with permission from Delihas © John Wiley and Sons.
Figure 5. Schematic of cleavage of sRNA and ompA and lamB target mRNAs by RNase III when the two RNAs are duplexed. Modified with permission from Viegas et al. © Oxford University Press.
Figure 6. (a) Diagrammatic representation of the E. coli rpoS mRNA showing the RBS sequestered by base pairing 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.Reproduced from Resch et al. © Cold Spring Harbor Laboratory Press for the RNA Society.


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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. DOI: 10.1111/j.1365-2958.2008.06394.x. PMID: 18710431.

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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. PMID: 18981732.

Additional Publications of Interest: sRNAs Associated with Bacterial Virulence:

Fris ME and Murphy ER (2016) Riboregulators: fine‐tuning virulence in Shigella. Frontiers in Cellular and Infection Microbiology 6: 2. DOI: 10.3389/fcimb.2016.00002. eCollection 2016. PMID: 26858941.

Lei S, Zhong Z, Ke Y, et al. (2016) Deletion of the small RNA chaperone protein Hfq down regulates genes related to virulence and confers protection against wild‐type Brucella challenge in mice. Frontiers in Microbiology 6: 1570. DOI: 10.3389/fmicb.2015.01570. eCollection 2015. PMID: 26834720.

Pitman S and Cho KH (2015) The mechanisms of virulence regulation by small noncoding RNAs in low GC Gram‐Positive pathogens. International Journal of Molecular Sciences 16: 29797–297814. DOI: 10.3390/ijms161226194. PMID: 26694351.

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Wang Y, Ke Y, Xu J, et al. (2005) Identification of a novel small non‐coding RNA modulating the intracellular survival of Brucella melitensis. Frontiers in Microbiology 6: 164. DOI: 10.3389/fmicb.2015.00164. eCollection 2015. PMID: 25852653.

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Delihas, Nicholas(Nov 2016) Small Regulatory RNAs in Bacteria. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000970.pub3]