Recent observations suggest that RNA-RNA interactions are decisive for bacterial virulence regulation and for adaptive stress responses needed for the survival in a host. This has been shown for the largest regulatory RNA, Staphylococcus aureus RNAIII (514 nts long), which controls the switch between the expression of surface proteins and excreted toxins. RNAIII plays a key role in the quorum sensing-dependent central regulatory circuit and coordinately regulates numerous virulence-associated genes (Novick, 2003). However, the mechanistic aspects of these regulations have been elucidated only for a few cases. We show that RNAIII coordinately represses the expression of mRNAs that encode a class of virulence factors acting early in the infection process. It acts as an antisense RNA and rapidly anneals to these mRNAs forming long RNA duplexes. The interaction between RNAIII and the mRNAs results in repression of translation initiation by blocking the access of the ribosome at its loading site and concomitantly triggers endoribonuclease III attack. In addition, RNAIII mediates translational repression of rot mRNA encoding for a transcriptional regulatory protein suggesting that RNAIII also indirectly acts on many downstream genes. The data emphasize the multitude of regulatory steps affected by RNAIII in establishing a network of S. aureus virulence factors (Boisset et al., 2007). Using different bioinformatic tools combined with expression studies, 10 novel non coding RNAs were identified in several clinical strains. Many of them accumulate at the late-exponential phase of growth, are stable, and are Hfq-independant. Four of these ncRNAs are specific for S. aureus, three are conserved in different staphylococcal strains. Only one is found in many bacillae, and is also expressed in Bacillus subtilis. Secondary structure mapping reveals that most of the ncRNAs carry a conserved sequence motif often presents in unpaired regions. These data argue for specific regulatory functions of the novel ncRNAs where several of them may act as antisense regulators.

- Novick, R.P. 2003. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 48: 1429-1449.
- Boisset S., Geissmann T et al. (2007) Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism. Genes & Dev. 21: 1353-1366.