Bacterial small RNA

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Bacterial small RNAs (sRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing 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), Streptococcus pyogenes, and the plant pathogen Xanthomonas oryzae pathovar oryzae.[3][4][5][6][7][8][9][10][11][12]

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.[13])


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.[14]


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 gene and the target gene, and trans-encoded sRNAs, where the antisense sRNA gene is separate from the target gene.[1][15]


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.[16][17]

Stress response[edit]

Many sRNAs are involved in stress response regulation.[18] They are expressed under stress conditions such as cold shock, iron depletion, onset of the SOS response and sugar stress.[17] The small RNA nitrogen stress-induced RNA 1 (NsiR1) is produced by Cyanobacteria under conditions of nitrogen deprivation.[19] Cyanobacteria NisR8 and NsiR9 sRNAs could be related to the differentiation of nitrogen-fixing cells (heterocysts).[20]

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.[17][21][22]

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.[23][24][25] 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.[23][26]


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;[14] 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.[17] The FasX sRNA is the only well-characterized regulatory RNA known to control the regulation of several virulence factors in Streptococcus pyogenes, including both cell-surface associated adhesion proteins as well as secreted factors.[27][28][29][30]

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.[31][32]

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,[33][34] IntaRNA,[34][35] TargetRNA[36] and RNApredator.[37] It has been shown that target prediction for enterobacterial sRNAs can benefit from transcriptome wide Hfq-binding maps.[38]


BSRD ( is a repository for published sRNA sequences with multiple valuable annotations and expression profiles.[39]

See also[edit]


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