Journal
ANNUAL REVIEW OF BIOPHYSICS, VOL 41
Volume 41, Issue -, Pages 343-370Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-biophys-101211-113224
Keywords
X-ray crystallography; ligand-binding pockets; NMR; RNA structure and folding; metal ions
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Funding
- NCI NIH HHS [P30 CA008748] Funding Source: Medline
- NIGMS NIH HHS [R01 GM034504, P41 GM066354, GM66354] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P30CA008748] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P41GM066354, R01GM034504] Funding Source: NIH RePORTER
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Riboswitches are mRNA elements capable of modulating gene expression in response to specific binding by cellular metabolites. Riboswitches exert their function through the interplay of alternative ligand-free and ligand-bound conformations of the metabolite-sensing domain, which in turn modulate the formation of adjacent gene expression controlling elements. X-ray crystallography and NMR spectroscopy have determined three-dimensional structures of virtually all the major riboswitch classes in the ligand-bound state and, for several riboswitches, in the ligand-free state. The resulting spatial topologies have demonstrated the wide diversity of riboswitch folds and revealed structural principles for specific recognition by cognate metabolites. The available three-dimensional information, supplemented by structure-guided biophysical and biochemical experimentation, has led to an improved understanding of how riboswitches fold, what RNA conformations are required for ligand recognition, and how ligand binding can be transduced into gene expression modulation. These studies have greatly facilitated the dissection of molecular mechanisms underlying riboswitch action and should in turn guide the anticipated development of tools for manipulating gene regulatory circuits.
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