Dethoff, E.A. et al. Nature advance online publication (7 October 2012).

Nuclear magnetic resonance (NMR) spectroscopy is a valuable tool for understanding the structural dynamics of proteins and RNA molecules, providing insights into their functions. To date, it has been possible to detect only relatively long-lived transition-state RNA species by NMR spectroscopy. However, short-lived, sparsely populated excited conformations of molecules are often key states for functions such as catalysis, molecular recognition or signaling. Borrowing and adapting a strategy previously developed to study protein excited states by NMR spectroscopy, Dethoff et al. now report a method to characterize RNA excited-state structures. The approach involves a combination of mutagenesis to stabilize candidate excited states, rotating frame carbon relaxation dispersion NMR experiments and secondary-structure prediction tools. Applying the method to three distinct RNAs, Dethoff et al. predict that RNA excited-state structures are common throughout the transcriptome.