Topology Links RNA Secondary Structure with Global Conformation, Dynamics, and Adaptation

Thermodynamic rules that link RNA sequences to secondary structure are well established, but the link between secondary structure and three-dimensional global conformation remains poorly understood. We constructed comprehensive three-dimensional maps depicting the orientation of A-form helices across RNA junctions in the Protein Data Bank and rationalized our findings with modeling and nuclear magnetic resonance spectroscopy. We show that the secondary structures of junctions encode readily computable topological constraints that accurately predict the three-dimensional orientation of helices across all two-way junctions. Our results suggest that RNA global conformation is largely defined by topological constraints encoded at the secondary structural level and that tertiary contacts and intermolecular interactions serve to stabilize specific conformers within the topologically allowed ensemble.