Elucidating the critical elements in folding and recognition of dynamic RNA structures remains a challenging problem. These challenges hinder efforts to understand RNA biology at the molecular level and to fully pursue RNA as a potential drug target. We have developed a method to use pattern-recognition of RNA with small molecules (PRRSM) to decipher patterns in RNA recognition as well as structural classification. In this application, we use aminoglycoside derivatives as receptors and fluorescently-labeled RNA constructs as analytes. This method allows for rapid assessment of patterns in small molecule:RNA recognition via plate reader measurements and principal component analysis, revealing similarities and differences in the recognition of distinct RNA structures. We have discovered that: 1) RNA secondary structure classes dictate the first level of classification, even with variation in sizes and sequences; 2) slightly denaturing conditions (PEG, 37°C) allow for increased differentiation of <i>individual</i> RNA constructs, presumably due to increased RNA dynamics; and 3) these classifications can be used to predict secondary structure at the fluorescently labeled site, leading to rapid observations of riboswitch conformational changes and revealing nucleotides critical for functional folding. We are currently expanding this procedure to include diverse small molecule scaffolds and more complex RNA structures.

Aminoglycoside receptors reveal patterns in RNA recognition and conformational change

256th National Meeting (2018)

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