Speaker
Description
Riboswitches are evolutionarily conserved RNA regulatory motifs that regulate gene expression by binding particular small-molecule ligands. Such native RNA sensors recognize metabolites or ions using their aptamer domains, whose structure changes upon ligand binding. This, in turn, causes structural changes in RNA folding that affect transcription termination, translation initiation, or RNA splicing. The aptamer region sequesters the ligand in a binding cleft through hydrogen bonding, base stacking, and metal ion coordination, imparting high specificity and affinity. Ligand-induced conformational changes stabilize RNA secondary structures within the expression platform, enabling sensitive and specific control of gene expression in response to metabolite levels.
The structural complexity of riboswitches is remarkable, with distinct classes adopting folds such as pseudoknots and multi-helix junctions, while still maintaining shared ligand-binding principles. Recent advances in X-ray crystallography, NMR, single-molecule fluorescence, and molecular dynamics simulations have provided insight into riboswitch folding pathways, binding kinetics, and conformational dynamics. Mechanistic models such as conformational selection and induced fit explain how riboswitches tune ligand affinity and regulatory responses.
Functionally, riboswitches often regulate bacterial metabolic pathways, ion transport, and stress responses, acting as ON or OFF switches depending on ligand availability. Their ability to regulate gene expression without protein cofactors highlights their efficiency. Beyond natural roles, riboswitches have been engineered in synthetic biology as ligand-inducible tools for metabolic engineering and biosensing. Therapeutically, riboswitches are promising antimicrobial targets since small-molecule analogs can disrupt essential bacterial gene regulation. Structural insights into riboswitch classes have enabled rational drug design.
Despite major progress, questions remain regarding riboswitch folding and ligand recognition under physiological conditions. Further discoveries of riboswitches across diverse organisms may uncover novel regulatory pathways and applications. Overall, riboswitches represent sophisticated RNA-based molecular sensors with high specificity and regulatory flexibility, with great promise in biotechnology, synthetic biology, and therapeutics.
