Co - Mentor
Understanding the cross-coupling of bacterial RNA polymerase and riboswitches
The folding of nascent transcripts is often modulated by properties of the transcribing RNA polymerase (RNAP). In particular, site-specific pausing of RNAP and co-transcriptional RNA-protein interactions have been shown in several cases to be important for co-transcriptional RNA folding. In bacteria, riboswitches are genetic elements frequently found in mRNA 5' untranslated regions, where they respond to cellular metabolites to regulate gene expression either at the level of transcription or translation. Since they change conformation as they are synthesized and bind their cognate ligand, riboswitches are tractable models for studying the role of the transcription process in guiding the folding of nascent transcripts, and vice versa. Using single molecule fluorescence approaches, the Walter group recently discovered that interactions with RNAP stabilize the native fold of a Bacillus subtilis preQ1 riboswitch, while binding of the preQ1 ligand signals RNAP release from a transcriptional pause. In collaboration with Dr. Melanie Ohi’s group, we are now using cryo-EM to study this novel cross-coupling in atomic detail. A postdoctoral fellow recruited as a linchpin for the collaboration will receive cross-disciplinary training and be involved in unveiling mechanistic insights into how transcription and RNA folding are co-regulated, forming a basis for discovering novel antibiotics.