PT - JOURNAL ARTICLE AU - Dalen Chan AU - Chao Feng AU - Whitney England AU - Dana Wyman AU - Ryan A. Flynn AU - Xiuye Wang AU - Yongsheng Shi AU - Ali Mortazavi AU - Robert C. Spitale TI - Transcriptome-Wide Combinatorial RNA Structure Probing in Living Cells AID - 10.1101/2020.03.24.006866 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.03.24.006866 4099 - http://biorxiv.org/content/early/2020/03/27/2020.03.24.006866.short 4100 - http://biorxiv.org/content/early/2020/03/27/2020.03.24.006866.full AB - RNA molecules can fold into complex structures and interact with trans-acting factors to control their biology. Recent methods have been focused on developing novel tools to measure RNA structure transcriptome-wide, but their utility to study and predict RNA-protein interactions or RNA processing has been limited thus far. Here, we extend these studies with the first transcriptomewide mapping method for cataloging RNA solvent accessibility, icLASER. By combining solvent accessibility (icLASER) with RNA flexibility (icSHAPE) data, we efficiently predict RNA-protein interactions transcriptome-wide and catalog RNA polyadenylation sites by RNA structure alone. These studies showcase the power of designing novel chemical approaches to studying RNA biology. Further, our study exemplifies merging complementary methods to measure RNA structure inside cells and its utility for predicting transcriptome-wide interactions that are critical for control of and regulation by RNA structure. We envision such approaches can be applied to studying different cell types or cells under varying conditions, using RNA structure and footprinting to characterize cellular interactions and processing involving RNA.