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  • Review Article
  • Published:

RNAs: regulators of bacterial virulence

Key Points

  • Bacterial pathogens have to respond rapidly to environmental conditions, and one way they achieve this is through regulatory RNAs.

  • 5′ untranslated regions (5′ UTRs) lie upstream of the coding sequence in mRNAs. The 5′ UTR can dictate the expression of the coding RNA by responding to environmental cues, directly altering its secondary structure.

  • 3′ UTRs lie downstream of the coding sequence and are thought to have regulatory functions.

  • Cis-acting antisense RNAs are encoded by the opposite strand of DNA to coding RNAs. These antisense RNAs might be complementary to the coding sequence or to the 3′ or 5′end of an mRNA transcript.

  • Trans-acting small non-coding RNAs are generally short and encoded in intergenic regions. They bind to distally located target mRNAs by direct base-pairing, thereby affecting protein expression, or they bind to regulatory proteins, modulating their activity.

  • Accessory proteins are required for many RNA-based regulatory systems. These include RNA chaperones (mainly Hfq), which stimulate RNA–RNA interactions, or RNases, which control the stability and/or maturity of specific transcripts.

Abstract

RNA-based pathways that regulate protein expression are much more widespread than previously thought. Regulatory RNAs, including 5′ and 3′ untranslated regions next to the coding sequence, cis-acting antisense RNAs and trans-acting small non-coding RNAs, are effective regulatory molecules that can influence protein expression and function in response to external cues such as temperature, pH and levels of metabolites. This Review discusses the mechanisms by which these regulatory RNAs, together with accessory proteins such as RNases, control the fate of mRNAs and proteins and how this regulation influences virulence in pathogenic bacteria.

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Figure 1: Control of mRNA activity and stability.
Figure 2: Untranslated region-mediated regulation.
Figure 3: Cis-acting antisense RNAs.
Figure 4: Trans-acting RNAs.

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Acknowledgements

J.G., S.N. and E.L. are supported by the J. C. Kempe foundation. A.T.-A. has a JAE-DOC research contract from Consejo Superior de Investigaciones Científicas (CSIC; the Spanish National Research Council). J.J. is supported by Umeå University, Sweden, by the Swedish Research Council grants 2008-58X-15144-05-3 and 621-2009-5677, and by European Research Council Starting Grant number 260764. We apologize to colleagues whose work could not be cited owing to space limitations.

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Glossary

Riboswitch

An mRNA control element that changes conformation in response to the binding of a metabolite (for example, glycine, lysine or coenzyme B12) and influences gene expression.

Shine–Dalgarno sequence

A sequence that is located 5′ of the AUG (start) codon on bacterial mRNAs and functions as the binding motif of the 30S subunit of the ribosome. The consensus sequence is AGGAGG.

Aptamer

An RNA domain, either engineered or natural, that forms a precise three-dimensional structure and selectively binds a target molecule.

Cyclic-di-GMP

A second messenger that is generated by diguanylate cyclases and hydrolysed by phosphodiesterase A.

Rho-independent transcriptional terminator

A strong secondary RNA structure followed by several uracils that destabilizes the RNA–DNA duplex so that the RNA polymerase falls off. Normally found after the coding sequence of an mRNA.

Response regulator

A bacterial gene-regulatory protein that controls gene expression in response to external signals. Most response regulators consist of two domains: a regulatory domain, the activity of which is modulated (indirectly) by the external signal, and a DNA-binding domain.

Transcriptional interference

The negative impact that one transcriptional activity can have on another transcriptional activity in cis.

Quorum sensing

The phenomenon in which the accumulation of signalling molecules enables a single cell to sense the number of bacteria that are present (the cell density); the purpose is to coordinate certain behaviours or actions between bacteria.

Degradosome

A complex of several proteins involved in the degradation and processing of various transcripts in Gram-negative bacteria.

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Gripenland, J., Netterling, S., Loh, E. et al. RNAs: regulators of bacterial virulence. Nat Rev Microbiol 8, 857–866 (2010). https://doi.org/10.1038/nrmicro2457

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