Sponging the system with RNA – modulating the levels, processing and efficacy of the key Gram-positive riboregulator of central metabolism RoxS
Metabolism operates as a highly integrated network that creates the energy and building blocks necessary for all cellular processes. Therefore, it is important that this process is optimally regulated. Bacteria have evolved elegant systems to enable rapid proliferation to take place when a preferred carbon source is available. This is well understood at the level of transcriptional regulation, but it was only relatively recently that the role of post-transcriptional factors began being recognised. RoxS has been identified as the key riboregulator of metabolism in Gram-positive species of bacteria and has been studied in molecular detail in Bacillus subtilis and Staphylococcus species. RoxS targets many mRNAs that encode proteins involved in metabolism. During a high-throughput approach to globally map pairwise RNA interactions in vivo using AMT crosslinking we identified a sRNA interacting with RoxS. We named this sRNA RosA (Regulator of sRNA A) and have shown that it acts as a RNA sponge under conditions where a preferred carbon source is not available. RosA is a highly processed sRNA that effects the fitness of the bacterium. Intriguingly, RosA not only acts to regulate the level of RoxS, but also its processing and efficacy. This additional post-transcriptional regulation adds a new level of control in correctly balancing the metabolic state of the cell.
Emma Denham completed a BSc in Genetics at the University of Leicester. Having discovered a passion for microbiology during the year she spent at the University of the Algarve, Portugal investigating autolysins in Helicobacter pylori, she moved to the then Institute for Animal Health, Compton, UK to complete her PhD under the supervision of Jamie Leigh and Phil Ward. There she investigated the lipoprotein processing enzymes in Streptococcus uberis. After completion of her PhD she moved to the lab of Jan Maarten van Dijl, University Medical Center Groningen, the Netherlands for her post-doctoral period. She switched bacterial species again, to study the Gram-positive model organism Bacillus subtilis and the pathogen Staphylococcus aureus. She was involved in several EU consortia, including BaSysBio and BaSynthec and became interested in all levels of regulation. During this time she developed a fascination with RNA and set about trying to understand how sRNAs fit within the B. subtilis regulatory network. In 2013 she started her own lab at the University of Warwick, UK and in 2018 she was made a Senior Lecturer of Microbiology at the University of Bath, UK where she continues to study RNA regulation in Gram-positive species.