Interrogating and Elucidating Drivers of Selective RNA-Ligand Interactions

Emily Swanson Hay, Ph.D. Candidate Amanda E. Hargrove Ph.D., Advisor Abstract: RNA has recently been recognized as a viable target for novel therapies. Subsequently, several studies have broadly investigated the properties of RNA binding small molecules. In this work, I will present novel efforts to understand the specific properties of small molecules that can recognize unique RNA structures. This question was explored first by evaluating the properties of known RNA-bioactive small molecules where we found that the number and types of ring systems strongly influenced recognition of different RNA structures. Secondly, a 15,000-member RNA-targeted library was evaluated for binding to nine distinct RNAs from three structural classes. Again, this identified unique properties for molecules that bind to different RNA structures, including the 3D shape of the small molecules. Finally, I will present work examining the specific recognition of RNA triple helices by a defined class of molecules from which a novel mechanism of binding was discovered.