LAUSR

Exciting discoveries of naturally occurring ligand-sensing and disease-linked noncoding RNAs have promoted significant interests in understanding RNA-small molecule interactions. NMR spectroscopy is a powerful tool for characterizing intermolecular interactions. In this review, we describe protocols and approaches for applying NMR spectroscopy to investigate interactions between RNA and small molecules. We review protocols for RNA sample preparation, methods for identifying RNA-binding small molecules, approaches for mapping RNA-small molecule interactions, determining complex structures, and characterizing binding kinetics. We hope this review will provide a guideline to streamline NMR applications in studying RNA-small molecule interactions, facilitating both basic mechanistic understandings of RNA functions and translational efforts in developing RNA-targeted therapeutics.