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BBB seminar: Daniel Lafontaine

Metabolite sensing in the TPP riboswitch is modulated during transcription elongation

Daniel Lafontaine
RNA Group, Department of Biology, Université de Sherbrooke, QC, Canada

Riboswitches are mRNA regulatory elements that modulate gene expression upon metabolite binding. These RNA switches control numerous basal metabolic pathways and have recently been shown to be powerful antimicrobial targets. Although riboswitch crystal structures have provided the basis for ligand recognition, their mechanisms of action have remained elusive, mostly due to the transient nature of riboswitch structural conformers. Our laboratory is interested in riboswitch folding mechanisms and how they are used to control gene expression in a metabolite-dependent manner. We have recently initiated the characterization of the thiamine pyrophosphate (TPP) sensing riboswitch that is involved in the cellular transport of TPP in E. coli. We find that transcription elongation complexes located at various naturally occurring pause sites within the TPP riboswitch differentially sense the presence of TPP. In particular, our data indicate that nascent riboswitch transcripts emanating from elongation complexes located at downstream positions do not efficiently sense TPP concentrations, thereby resulting in a small transcriptional window in which TPP sensing is efficiently performed. Using a combination of biochemical and single-molecule assays, we are currently investigating the structure of each riboswitch transcript species along the transcriptional pathway. This work will shed light on the riboswitch co-transcriptional TPP sensing and how this is ultimately involved in the regulation of gene expression.

Chairperson: Ruth Brenk, Department of Biomedicine