Laboratory of Post-Transcriptional Control of Gene Expression

Adaptability is one of the essential features of microorganisms allowing them to endure and thrive within a wide range of environmental conditions. In order to adapt, bacteria must rapidly and efficiently alter their gene expression in response to environmental stimuli. This can be accomplished by regulating the gene transcription with sigma factors and transcriptional activators or repressors. Nevertheless, gene expression can be modulated after transcription is initiated and this post-transcriptional regulation is a key controlling mechanism allowing fast and appropriate adaptation. The regulatory elements involved in post-transcriptional regulation include among others RNA-binding proteins, RNases, small regulatory RNAs (sRNAs), riboswitches and typically affect the mRNA stability and decay and translational efficiency at both initiation and elongation steps.

Bacterial trans-encoded sRNAs represent the major class of non-coding RNAs and were shown to play important role in post-transcriptional regulation of many genes including those involved in virulence. Base-pairing of sRNAs with their cognate mRNA targets results in either repression or activation of translation. In Gram-negative bacteria the sRNA-mRNA interaction is mediated by RNA chaperone Hfq which simultaneously binds both RNA molecules and facilitates this riboregulatory mechanism. Hfq binding also affects the stability of sRNA and mRNA transcripts. Therefore, Hfq plays a central role in post-transcriptional regulation in a large numbers of microorganisms.

We focus on Hfq and sRNA-mediated post-transcriptional mechanisms employed by human pathogen Bordetella pertussis. We have shown that the hfq mutant is clearly attenuated in the mouse respiratory model of infection as its lethality as well as its capacity to colonize mouse lungs is strongly reduced when compared to the wt strain. Furthermore, the loss of Hfq has a profound effect on gene expression in B. pertussis. Comparative transcriptional profiling revealed that Hfq is required for expression of several virulence factors in B. pertussis cells including the Type III secretion system (T3SS). In collaboration with our colleagues from Vienna and Lille we have identified and described several sRNAs. Currently we aim at functional characterization of these sRNAs and elucidation of their role in physiology and virulence of B. pertussis.