Elucidating the Evolution and Function of sRNAs that Facilitate Bacterial Stress Tolerance

Non-coding small RNAs (sRNAs) are ubiquitous post-transcriptional regulators found in both gram-negative and gram-positive bacteria. Despite their integral role in many regulatory pathways, including those that facilitate stress-tolerance, little is known about the evolutionary forces that drive the emergence of novel sRNAs, how prevalent sRNAs are within bacterial species, or the functions of a majority of these transcripts. In this work, I first describe the evolution of OxyS, a well-characterized sRNA in gram-negative Enterobacteriaceae that is involved in coordinating the bacterial response to oxidative stress. Next, I identify novel sRNAs differentially produced by the gram-positive oral pathogen Streptococcus mutans in response to multiple stress conditions. Finally, I investigate the function of one novel sRNA, SmsR4, in fine-tuning sugar-alcohol metabolism in S. mutans. These findings reveal protein coding genes to be a new reservoir for sRNA emergence and define a novel evolutionary path through which new sRNAs become incorporated into regulatory networks. Additionally, I show evidence for abundant regulation by sRNAs in S. mutans during a variety of stress responses and outline how SmsR4 participates in the regulation of sugar metabolism. Taken together, this work presents a new paradigm for sRNA emergence from protein coding genes and demonstrates the prevalence and utility of the understudied phenomenon of post-transcriptional regulation in oral bacteria