Ligand-observed NMR techniques to probe RNA-small molecule interactions.

Abstract

A growing understanding of the structure and function of RNA has revealed it as a key regulator of gene expression and disease. A multitude of noncoding functions apart from the central roles of RNA in coding for and facilitating protein biogenesis has stimulated research into RNA as a pharmacological target. Despite many exciting advances, RNA remains an understudied target for small molecules, and techniques to investigate RNA-binding molecules are still emerging. A key stumbling block in this area has been validation of RNA-small molecule interactions. Our laboratory has recently used multiple ligand-observed NMR techniques in this regard, including CPMG and WaterLOGSY. This work describes methods to use these techniques in the context of studying RNA-ligand interactions.