The PreQ1 Riboswitch
Riboswitches are structured RNA elements present in the 5’ untranslated regions of some mRNAs and regulate gene expression via pre-mature transcription termination or repression of translation initiation (Fig. 1). They achieve this simply by changing conformation upon binding the ligand, which could be a metabolite, vitamin, metal ion, nucleotide, amino acid etc. Riboswitches are ubiquitous in bacteria, including some pathogens, and they are actively pursued as potential therapeutic targets. The PreQ1 riboswitch is the smallest known naturally occurring riboswitch with just 34 nucleotides required for substrate binding. It has very high affinity for the ligand PreQ1 (Kd ~ 50 nM) which is required for translational fidelity in many bacteria. The preQ1 riboswitch presents an interesting case of high affinity substrate recognition by a small RNA motif. Understanding the structural dynamics of the PreQ1 riboswitch will give some insight into the mechanism of its conformational ‘switch’ and could also help in designing better drugs against pathogens which contain PreQ1 riboswitch. We are using single molecule fluorescence resonance energy transfer (smFRET) microscopy to understand the conformational dynamics of the PreQ1 riboswitch. This work is being done in collaboration with Prof. Hashim Al-Hashimi, Prof. Charles L. Brooks and Prof. George Garcia.