irCLASH reveals RNA substrates recognized by human ADARs
- 23 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 27 (4), 351-362
- https://doi.org/10.1038/s41594-020-0398-4
Abstract
Adenosine deaminases acting on RNA (ADARs) convert adenosines to inosines in double-stranded RNA (dsRNA) in animals. Despite their importance, ADAR RNA substrates have not been mapped extensively in vivo. Here we develop irCLASH to map RNA substrates recognized by human ADARs and uncover features that determine their binding affinity and editing efficiency. We also observe a dominance of long-range interactions within ADAR substrates and analyze differences between ADAR1 and ADAR2 editing substrates. Moreover, we unexpectedly discovered that ADAR proteins bind dsRNA substrates tandemly in vivo, each with a 50-bp footprint. Using RNA duplexes recognized by ADARs as readout of pre-messenger RNA structures, we reveal distinct higher-order architectures between pre-messenger RNAs and mRNAs. Our transcriptome-wide atlas of ADAR substrates and the features governing RNA editing observed in our study will assist in the rational design of guide RNAs for ADAR-mediated RNA base editing.This publication has 67 references indexed in Scilit:
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