Genetic regulation mechanism of the yjdF riboswitch

The yjdF riboswitch resides in potential 5' UTRs of homologues of protein-coding gene yjdF in Firmicutes. Unlike other 30 riboswitch classes previously validated, this riboswitch class, can sense and bind to a broad collection of azaaromatic ligands. Among these compounds, some do activate production of yjdF protein driven by the riboswitch, while others are out of riboswitch-mediated modulation possibly because of the toxicity at high ligand concentrations. By incorporating the structures with pseudoknots and ligand binding kinetics into the co-transcriptional folding theory, we theoretically studied the co-transcriptional folding behaviors of the yjdF riboswitch from Bacillus subtilis at different transcription conditions. Like most riboswitches, the yjdF riboswitch can quickly fold into the aptamer structure without any trapped states during the transcription process. After the aptamer structure is formed, the riboswitch shows two main co-transcriptional folding pathways: aptamer→ON state→OFF state and aptamer → the ligand bound aptamer → the ligand bound ON state. Our results suggested that this translational riboswitch is coupled with the transcription process to exert its biological function and it is kinetically controlled. The threshold concentration for the ligand to activate the riboswitch depends on the transcription rate and the association rate of the ligand binding.