RNA molecules perform essential cellular functions including gene regulation, protein synthesis, and genome defense. These diverse biochemical activities frequently depend on RNA secondary and tertiary structures that begin to fold during transcription. An RNA sequence can therefore be constrained by its coding potential, by its functional structure, and by the need to fold correctly.
Understanding the interdependence of these constraints is essential for predicting how changes in an RNA sequence affect its structure, and ultimately its biological function. Because all RNAs can begin to fold when they are transcribed, our ability to predict how RNA folds cotranscriptionally is important for our basic understanding of RNA-mediated biological processes, the development of synthetic RNA tools, and our knowledge of human disease states. We study the basic mechanisms through which cotranscriptional RNA folding mediates gene regulation and RNA biogenesis by developing and applying high-throughput approaches for measuring nascent RNA structure and function.