GL08

I will present examples of RNA-elements, illustrate how we have characterised these in more detail and discuss how they may be involved in sensing and adapting to the host environment.

The last few decades have demonstrated how the exquisite versatility of RNA has placed this molecule at the centre of gene expression. In addition to mediating and catalysing protein synthesis via mRNA, tRNA and rRNA, regulatory RNAs ensure that the processes of transcription and translation are carried out with optimal accuracy and efficiency.

Regulatory RNAs, i.e. sRNAs and riboswitches, have emerged as major contributors to gene expression control in model organisms, but the rules of engagement remain obscure in Mycobacterium tuberculosis, and more than a decade after the first identification of M. tuberculosis sRNAs, we know preciously little about their MO. RNA-seq has facilitated the identification of sRNAs and their expression patterns, and while we do know that many of these, e.g. DrrS and F6, are upregulated during infection indicating a role in pathogenesis, we do not know how they control their targets.  

Our knowledge about M. tuberculosis RNA leaders/riboswitches is even more scarce. A few elements show similarity to known riboswitches, and their cognate ligands such as cobalamin, glycine and Mg²⁺ are known, but how ligand-binding decodes into changes in gene expression and how that affects host-pathogen interactions, remains to be determined. Moreover, our results using RNA-seq and Term-seq have identified additional RNA leaders with unknown ligands that may be involved in pathogenesis and, in case of the RpfB-switch, resuscitation from dormancy.