Global Discovery of Small Noncoding RNAs in Pathogenic Yersinia Species
Small noncoding RNAs (sRNAs) function as regulatory elements in both eukaryotes and bacteria. Trans-acting bacterial sRNAs posttranscriptionally regulate gene expression by base pairing with target mRNAs, which often leads to changes in translation efficiency and/or stability of the transcript. Bioinformatic search algorithms along with a variety of experimental approaches have become increasingly useful for the discovery of sRNAs and their mRNA targets. Our laboratory and others recently demonstrated that Hfq, a protein chaperone of sRNAs in bacteria, is required for the full virulence of both Yersinia pestis, the bacterium that causes the disease plague, and the genetically related gastrointestinal pathogen Yersinia pseudotuberculosis. This led us to pursue the first global identification and analysis of sRNAs in pathogenic Yersinia species. We have identified 150 previously unannotated sRNAs expressed by Y. pseudotuberculosis when cultured in vitro at either 26°C or 37°C, the majority of which are Yersinia-specific. The deletion of multiple Yersinia-specific sRNAs from either Y. pseudotuberculosis or Y. pestis leads to the attenuation of these pathogens in mouse models of infection. In addition, we have identified the mRNA targets controlled by one of these virulence-associated sRNAs, suggesting potential new virulence determinants in Y. pseudotuberculosis.
We thank Trevis Alleyne for assistance with bioinformatics analysis of the deep sequencing data, Chelsea Schiano for contributing reagents, and Lauren Bellows for technical assistance. This work was sponsored by the Northwestern University Feinberg School of Medicine and the NIH/NIAID Regional Center of Excellence for Bio-defense and Emerging Infectious Diseases Research (RCE) Program. We also acknowledge membership within and support from the Region V “Great Lakes” RCE (NIH award U54 AI057153).
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