Regulation of Heterogenous LexA Expression in Staphylococcus aureus by an Antisense RNA Originating from Transcriptional Read-Through upon Natural Mispairings in the sbrB Intrinsic Terminator.

Bacterial genomes are pervasively transcribed, generating a wide variety of antisense RNAs (asRNAs). Many of them originate from transcriptional read-through events (TREs) during the transcription termination process. Previous transcriptome analyses revealed that the lexA gene from Staphylococcus aureus , which encodes the main SOS response regulator, is affected by the presence of an asRNA. Here, we show that the lexA antisense RNA ( lexA -asRNA) is generated by a TRE on the intrinsic terminator (TT _sbrB ) of the sbrB gene, which is located downstream of lexA , in the opposite strand. Transcriptional read-through occurs by a natural mutation that destabilizes the TT _sbrB structure and modifies the efficiency of the intrinsic terminator. Restoring the mispairing mutation in the hairpin of TT _sbrB prevented lexA -asRNA transcription. The level of lexA -asRNA directly correlated with cellular stress since the expressions of sbrB and lexA -asRNA depend on the stress transcription factor SigB. Comparative analyses revealed strain-specific nucleotide polymorphisms within TT _sbrB , suggesting that this TT could be prone to accumulating natural mutations. A genome-wide analysis of TREs suggested that mispairings in TT hairpins might provide wider transcriptional connections with downstream genes and, ultimately, transcriptomic variability among S. aureus strains.