Prokaryotic mRNAs have short half-lives which allow rapid changes to the transcriptome. The processing of an mRNA may be directed, enhanced, or inhibited by direct base-pairing of regulatory small RNA (sRNA), which have emerged as ubiquitous gene regulators in bacterial species. Regulatory sRNAs litter the bacterial transcriptome and have been most extensively characterised in the model Gammaproteobacteria E. coli and Salmonella but characterisation of these regulatory RNAs has lagged in Gram-positive species. To capture in vivo RNA-RNA interactions associated with the double-stranded RNA-specific endonuclease RNase III we utilised RNase III-CLASH (UV-crosslinking, ligation and sequencing of hybrids), and to accurately map these interactions to transcriptome features we used dRNA-seq and Term-seq techniques in the methicillin-resistant Staphylococcus aureus (MRSA) isolate JKD6009. We uncovered hundreds of novel sRNA-mRNA interactions allowing functional characterisation of many sRNAs for the first time. Surprisingly, we recovered 543 statistically significant mRNA-mRNA interactions. We find that an mRNA encoding an unusually long 3’UTR (here termed vigR-3’UTR) functions as a regulatory ‘hub’ required for MRSA virulence in a wax moth model of infection, and for vancomycin tolerance. We also uncovered novel mRNA-mRNA interactions within the yabJ-spoVG bicistronic operon involved in methicillin resistance. We confirmed a direct mRNA-mRNA interaction that seemingly allows sub-operonic control of yabJ and spoVG expression. Our results demonstrate the utility of CLASH for identifying new regulatory RNA and indicate for the first time the extensive use of mRNA-mRNA interactions in a prokaryote to coordinate gene expression.