COMRADES determines in vivo RNA structures and interactions

RNA structural flexibility underlies fundamental biological processes, but there are no methods to explore the multiple conformations adopted by RNAs in vivo. We developed Crosslinking Of Matched RNAs And Deep Sequencing (COMRADES) for in-depth RNA conformation capture, and a pipeline for retrieval of RNA structural ensembles. Using COMRADES, we determined the architecture of the Zika virus RNA genome inside cells, and revealed multiple site-specific interactions with human non-coding RNAs.