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A cis-encoded RNA interaction controls sub-operonic spoVG expression in Staphylococcus aureus

Lynch, R.; Pettersson, M.; Coulon, P. M. L.; Biazik, J. M.; Tree, J. J.; Mediati, D. G.

2026-09-19 microbiology
10.64898/2026.09.18.752551 bioRxiv
Show abstract

Bacterial operons enable co-transcription of multiple genes, yet post-transcriptional mechanisms permitting differential regulation of individual genes within a polycistronic transcript remains incompletely understood. We demonstrate that a cis-encoded RNA-RNA interaction within the bicistronic yabJ-spoVG transcript forms an RNase III substrate that represses the transcription factor SpoVG in Staphylococcus aureus. Disruption of the cis-encoded regulation elevated monocistronic spoVG expression, reduced biofilm formation and cell wall peptidoglycan thickness, and increased sensitivity to cell wall-targeting antimicrobials in clinical vancomycin-intermediate S. aureus, consistent with phenotypes observed in an independent SpoVG overexpression strain. These findings uncover a previously undescribed mode of cis-regulatory control within a polycistronic operon and establish regulatory mRNA-mRNA interactions as a mechanism for sub-operonic gene regulation.

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