Rsa RNA explained

Rsa RNAs are non-coding RNAs found in the bacterium Staphylococcus aureus. The shared name comes from their discovery, and does not imply homology. Bioinformatics scans identified the 16 Rsa RNA families named RsaA-K and RsaOA-OG.^{[1] [2]} Others, RsaOH-OX, were found thanks to an RNomic approach.^[3] Although the RNAs showed varying expression patterns, many of the newly discovered RNAs were shown to be Hfq-independent and most carried a C-rich motif (UCCC).

RsaA

Represses the translation of the transcriptional regulator MgrA by binding to its mRNA, enhances biofilm formation and decreases bacterial virulence.^[4] Other mRNAs: including SsaA-like enzymes involved in peptidoglycan metabolism and the secreted anti-inflammatory FLIPr protein were validated as direct targets of RsaA.^[5]

RsaE

RsaE is found in other members of the genus Staphylococcus such as Staphylococcus epidermidis and Staphylococcus saprophyticus and is the only Rsa RNA to be found outside of this genus, in Macrococcus caseolyticus and Bacillus. In Bacillus subtilis, RsaE had previously been identified as ncr22.^{[6] [7]} RsaE is also consistently found downstream of PepF which codes for oligoendopeptidase F. The function of RsaE was discovered using gene knockout analysis and gene overexpression - it was found to regulate the expression of several enzymes involved in metabolism via antisense binding of their mRNA.

RsaE was shown to be regulated by the presence of nitric oxide (NO). In Bacillus subtilis it controls expression of genes with functions related to oxidative stress and oxidation-reduction reactions and it was renamed RoxS (for related to oxidative stress).^[8]

RsaF

In S.aureus species RsaF is located in the same intergenic region as RsaE and overlaps with 3′ end of RsaE by approximately 20bp. In contrast to RsaE, RsaF and its upstream gene have only been identified in S.aureus species.

RsaK

RsaK is found in the leader sequence of glcA mRNA which encodes an enzyme involved in the glucose-specific phosphotransferase system. RsaK also contains a conserved ribonucleic antiterminator system, as recognised by GclT protein.^[9]

RsaI

RsaOG also renamed RsaI is thought to fine-tune the regulation of toxin or invasion mechanisms in S. aureus via trans-acting mechanisms. Its secondary structure contains a pseudoknot formed between two highly conserved unpaired sequences.

Expression patterns

RsaD, E H and I were found to be highly expressed in S. aureus. Expression levels of other Rsa RNAs varied under various environmental conditions, for example RsaC was induced by cold shock and RsaA is induced in response to osmotic stress.

RsaE and RsaF genes overlap in S.aureus species but appear to have opposite expression patterns. Transcriptional interference due to an overlap between a σ^A recognition motif and a potential σ^B binding site is proposed as a mechanism causing the differential expression of the two transcripts^[10]

See also

• RsaOG

Further reading

• Pichon C, Felden B . Small RNA genes expressed from Staphylococcus aureus genomic and pathogenicity islands with specific expression among pathogenic strains . Proceedings of the National Academy of Sciences of the United States of America . 102 . 40 . 14249–14254 . October 2005 . 16183745 . 1242290 . 10.1073/pnas.0503838102 . free .
• Altuvia S . Identification of bacterial small non-coding RNAs: experimental approaches . Current Opinion in Microbiology . 10 . 3 . 257–261 . June 2007 . 17553733 . 10.1016/j.mib.2007.05.003 .
• Morfeldt E, Taylor D, von Gabain A, Arvidson S . Activation of alpha-toxin translation in Staphylococcus aureus by the trans-encoded antisense RNA, RNAIII . The EMBO Journal . 14 . 18 . 4569–4577 . September 1995 . 7556100 . 394549 . 10.1002/j.1460-2075.1995.tb00136.x.
• Roberts C, Anderson KL, Murphy E, Projan SJ, Mounts W, Hurlburt B, Smeltzer M, Overbeek R, Disz T, Dunman PM . Characterizing the effect of the Staphylococcus aureus virulence factor regulator, SarA, on log-phase mRNA half-lives . Journal of Bacteriology . 188 . 7 . 2593–2603 . April 2006 . 16547047 . 1428411 . 10.1128/JB.188.7.2593-2603.2006 .
• Anderson KL, Roberts C, Disz T, Vonstein V, Hwang K, Overbeek R, Olson PD, Projan SJ, Dunman PM . Characterization of the Staphylococcus aureus heat shock, cold shock, stringent, and SOS responses and their effects on log-phase mRNA turnover . Journal of Bacteriology . 188 . 19 . 6739–6756 . October 2006 . 16980476 . 1595530 . 10.1128/JB.00609-06 .
• Huntzinger E, Boisset S, Saveanu C, Benito Y, Geissmann T, Namane A, Lina G, Etienne J, Ehresmann B, Ehresmann C, Jacquier A, Vandenesch F, Romby P . Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression . The EMBO Journal . 24 . 4 . 824–835 . February 2005 . 15678100 . 549626 . 10.1038/sj.emboj.7600572 .
• Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S . Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule . The EMBO Journal . 12 . 10 . 3967–3975 . October 1993 . 7691599 . 413679 . 10.1002/j.1460-2075.1993.tb06074.x.
• Bohn C, Rigoulay C, Bouloc P . No detectable effect of RNA-binding protein Hfq absence in Staphylococcus aureus . BMC Microbiology . 7 . 10 . February 2007 . 17291347 . 1800855 . 10.1186/1471-2180-7-10 . free .

Notes and References

1. Geissmann T, Chevalier C, Cros MJ, Boisset S, Fechter P, Noirot C, Schrenzel J, François P, Vandenesch F, Gaspin C, Romby P . A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation . Nucleic Acids Research . 37 . 21 . 7239–7257 . November 2009 . 19786493 . 2790875 . 10.1093/nar/gkp668 .
2. Marchais A, Naville M, Bohn C, Bouloc P, Gautheret D . Single-pass classification of all noncoding sequences in a bacterial genome using phylogenetic profiles . Genome Research . 19 . 6 . 1084–1092 . June 2009 . 19237465 . 2694484 . 10.1101/gr.089714.108 .
3. Bohn C, Rigoulay C, Chabelskaya S, Sharma CM, Marchais A, Skorski P, Borezée-Durant E, Barbet R, Jacquet E, Jacq A, Gautheret D, Felden B, Vogel J, Bouloc P . Experimental discovery of small RNAs in Staphylococcus aureus reveals a riboregulator of central metabolism . Nucleic Acids Research . 38 . 19 . 6620–6636 . October 2010 . 20511587 . 2965222 . 10.1093/nar/gkq462 .
4. Romilly C, Lays C, Tomasini A, Caldelari I, Benito Y, Hammann P, Geissmann T, Boisset S, Romby P, Vandenesch F . A non-coding RNA promotes bacterial persistence and decreases virulence by regulating a regulator in Staphylococcus aureus . PLOS Pathogens . 10 . 3 . e1003979 . March 2014 . 24651379 . 3961350 . 10.1371/journal.ppat.1003979 . free .
5. Tomasini A, Moreau K, Chicher J, Geissmann T, Vandenesch F, Romby P, Marzi S, Caldelari I . The RNA targetome of Staphylococcus aureus non-coding RNA RsaA: impact on cell surface properties and defense mechanisms . Nucleic Acids Research . 45 . 11 . 6746–6760 . June 2017 . 28379505 . 5499838 . 10.1093/nar/gkx219 .
6. Rasmussen S, Nielsen HB, Jarmer H . The transcriptionally active regions in the genome of Bacillus subtilis . Molecular Microbiology . 73 . 6 . 1043–1057 . September 2009 . 19682248 . 2784878 . 10.1111/j.1365-2958.2009.06830.x .
7. Irnov I, Sharma CM, Vogel J, Winkler WC . Identification of regulatory RNAs in Bacillus subtilis . Nucleic Acids Research . 38 . 19 . 6637–6651 . October 2010 . 20525796 . 2965217 . 10.1093/nar/gkq454 .
8. Durand S, Braun F, Lioliou E, Romilly C, Helfer AC, Kuhn L, Quittot N, Nicolas P, Romby P, Condon C . A nitric oxide regulated small RNA controls expression of genes involved in redox homeostasis in Bacillus subtilis . PLOS Genetics . 11 . 2 . e1004957 . February 2015 . 25643072 . 4409812 . 10.1371/journal.pgen.1004957 . free .
9. Langbein I, Bachem S, Stülke J . Specific interaction of the RNA-binding domain of the bacillus subtilis transcriptional antiterminator GlcT with its RNA target, RAT . Journal of Molecular Biology . 293 . 4 . 795–805 . November 1999 . 10543968 . 10.1006/jmbi.1999.3176 .
10. Shearwin KE, Callen BP, Egan JB . Transcriptional interference—a crash course . Trends in Genetics . 21 . 6 . 339–345 . June 2005 . 15922833 . 2941638 . 10.1016/j.tig.2005.04.009 .