RNA base-pairing complexity in living cells visualized by correlated chemical probing
Abstract
How do we determine the structure of an RNA, particularly in cells? Chemical probing is a broadly applicable strategy for mapping RNA structure. However, chemical probing experiments do not observe base pairs directly and hence are unable to unambiguously define global RNA structure or resolve structural dynamics. We describe an approach, PAIR-MaP, that harnesses correlations in how nucleotides are chemically modified to simultaneously map local RNA structure and directly detect base pairs. PAIR-MaP visualizes long-range helices and pseudoknots in complex RNAs with high specificity and resolution, including in living cells, and further reveals alternative base-pairing states. PAIR-MaP makes it possible to determine RNA structure and dynamics in cells with high resolution, confidence, and throughput.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2019
- DOI:
- 10.1073/pnas.1905491116
- Bibcode:
- 2019PNAS..11624574M