Real-time multidimensional NMR follows RNA folding with second resolution.
Conformational transitions and structural rearrangements are central to the function of many RNAs yet remain poorly understood. We have used ultrafast multidimensional NMR techniques to monitor the adenine-induced folding of an adenine-sensing riboswitch in real time, with nucleotide-resolved resolution. By following changes in 2D spectra at rates of approximately 0.5 Hz, we identify distinct steps associated with the ligand-induced folding of the riboswitch. Following recognition of the ligand, long range loop-loop interactions form and are then progressively stabilized before the formation of a fully stable complex over approximately 2-3 minutes. The application of these ultrafast multidimensional NMR methods provides the opportunity to determine the structure of RNA folding intermediates and conformational trajectories.
Lee
Mi-Kyung
MK
Department of Chemistry, University of Washington, Box 351700, Seattle WA 98195, USA.
Gal
Maayan
M
Frydman
Lucio
L
Varani
Gabriele
G
D000225:Adenine / Q000378:metabolism; D020029:Base Pairing; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics* / Q000502:physiology; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics* / Q000502:physiology; D013997:Time Factors
D038621:Regulatory Sequences, Ribonucleic Acid; D012313:RNA; D000225:Adenine