Regulation of OmpA Translation and Shigella dysenteriae Virulence by an RNA Thermometer.

RNA thermometers are -acting riboregulators that mediate the posttranscriptional regulation of gene expression in response to environmental temperature. Such regulation is conferred by temperature-responsive structural changes within the RNA thermometer that directly result in differential ribosomal binding to the regulated transcript. The significance of RNA thermometers in controlling bacterial physiology and pathogenesis is becoming increasingly clear. This study combines , molecular genetics, and biochemical analyses to characterize both the structure and function of a newly identified RNA thermometer within the transcript of First identified by structural predictions, genetic analyses have demonstrated that the RNA thermometer is a functional riboregulator sufficient to confer posttranscriptional temperature-dependent regulation, with optimal expression observed at the host-associated temperature of 37°C. Structural studies and ribosomal binding analyses have revealed both increased exposure of the ribosomal binding site and increased ribosomal binding to the transcript at permissive temperatures. The introduction of site-specific mutations predicted to alter the temperature responsiveness of the RNA thermometer has predictable consequences for both the structure and function of the regulatory element. Finally, tissue culture-based analyses implicate the RNA thermometer as a bona fide virulence factor in this bacterial pathogen. Given that is highly conserved among Gram-negative pathogens, these studies not only provide insight into the significance of riboregulation in controlling virulence, but they also have the potential to facilitate further understanding of the physiology and/or pathogenesis of a wide range of bacterial species.