Fig. 6: Models for ligand-dependent transcription regulation by the fluoride riboswitch.

(a) A proposed local conformational change at early transcript length, where F^- binding pre-organizes the aptamer by poising the 5’ segment of the pseudoknot in close proximity to the RNAP exit channel, facilitating pseudoknot formation once the 3’ segment is transcribed. (b) If F^- binds late, the aptamer is highly dynamic in nature in the absence of Mg²⁺, transitioning among the prefolded, folded and unfolded states. The unfolded state is prevalent when the aptamer has been transcribed completely and the A40-U48 interaction can occur (RNA64). In the presence of physiological Mg²⁺ concentrations, the riboswitch dynamically samples a docked conformation similar to the ligand-bound conformation (“dynamic docked”). The binding of F^- stabilizes this conformation (to become “stably docked”), mediated by the linchpin long-range A40-U48 interaction.