The promise of cryo-EM to explore RNA structural dynamics

Conformational dynamics are essential to macromolecular function. This is certainly true of RNA, whose ability to undergo programmed conformational dynamics is essential to create and regulate complex biological processes. However, methods to easily and simultaneously interrogate both the structure and conformational dynamics of fully functional RNAs in isolation and in complex with proteins have not historically been available. Due to its ability to image and classify single particles, cryogenic electron microscopy (cryo-EM) has the potential to address this gap and may be particularly amenable to exploring structural dynamics within the three-dimensional folds of biologically active RNAs. We discuss the possibilities and current limitations of applying cryo-EM to simultaneously study RNA structure and conformational dynamics, and present one example that illustrates this (as of yet) not fully realized potential.