RNA exhibits considerable structural and functional diversity beyond well established roles of ribosomal, transfer and messenger RNAs, as illustrated by the discovery of ever increasing numbers of diverse RNA structures involved in gene processing and regulation. RNA molecules are often quite flexible; they can function in a genuinely unfolded form and adapt for recognition of both the shape and the charge distribution on a potential ligand with exquisite specificity. Liquid state NMR spectroscopy is uniquely suited to answer important questions concerning biophysical properties of RNA molecules including their three-dimensional shape, secondary structure distribution, and flexibility by looking at dynamic ensembles of structures. Here we review the fields of RNA sample preparation and NMR methodology that facilitate the determination of RNA structure in solution.
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