RNA Structural Differentiation: Opportunities with Pattern Recognition

Our awareness and appreciation of the many regulatory roles of RNA have dramatically increased in the past decade. This understanding, in addition to the impact of RNA in many disease states, has renewed interest in developing selective RNA-targeted small molecule probes. However, the fundamental guiding principles in RNA molecular recognition that could accelerate these efforts remain elusive. While high-resolution structural characterization can provide invaluable insight, examples of well-characterized RNA structures, not to mention small molecule:RNA complexes, remain limited. This Perspective provides an overview of the current techniques used to understand RNA molecular recognition when high-resolution structural information is unavailable. We will place particular emphasis on a new method, pattern recognition of RNA with small molecules (PRRSM), that provides rapid insight into critical components of RNA recognition and differentiation by small molecules as well as into RNA structural features.