Molecular regulation of bacterial genes by small RNA molecules during cellular growth phases

Small non-coding RNAs (sRNAs) are a class of regulatory molecules that modulate a wide range of cellular processes. sRNA molecules have been shown to regulate gene expression and protein production through transcriptional or translational regulation and/or mRNA stability. The ability to regulate these diverse processes underscores the key regulatory role of sRNAs in bacterial growth and replication. Traditionally, these processes have been characterized in vitro through examining the effects on cellular growth phases in bacteria.;The early description of small stable RNA (SSR) molecules in Staphylococcus aureus were based on mRNA turnover studies by Dunman and associates. Collectively, 142 SSRs were found to be expressed in S. aureus when subjected to various growth and stress conditions. We hypothesize that the stable sRNA molecules play a direct role in affecting genes during the transitioning of growth phases. To characterize these SSRs, the transcriptional units were defined by utilizing 5' and 3' Rapid Amplification of cDNA Ends. The transcriptional units were compared to S. aureus genomes in the National Institute Center for Biotechnology Information database. Two SSRs were highly conserved and the transcriptional profiles suggested that these RNA molecules were significantly expressed during stationary phase growth. Therefore, SSR91 and SSR42 were selected as candidates to investigate the role of SSRs in growth dependent regulation of S. aureus. Exploratory studies were initiated in Francisella tularensis, another important human pathogen. F. tularensis is an intracellular zoonotic bacterium that is transmitted by insects. As such, it must rapidly adapt to multiple environmental conditions. We therefore hypothesized that SSRs would play a role in the ability of this organism to transition between growth phases. The transcriptomes of two F. tularensis subspecies were monitored throughout growth and a total of 17 putative sRNAs were discovered. Future studies will most likely reveal the importance and universality of SSR regulatory processes in bacteria. Long term, it is expected that these studies will reveal novel targets for antimicrobial discovery or immune regulation.