期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 27, 期 4, 页码 351-+出版社
NATURE RESEARCH
DOI: 10.1038/s41594-020-0398-4
关键词
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资金
- National Key Research and Development Program of China [2018YFC1003100]
- Guangdong Major Science and Technology Projects [2017B020226002]
- Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S638]
- National Natural Science Foundation of China [31571341, 91631108, 31900437]
- Fundamental Research Funds for the Central Universities
- Common Fund of the Office of the Director of the National Institutes of Health
- National Cancer Institute (NCI)
- National Human Genome Research Institute (NHGRI)
- National Heart, Lung, and Blood Institute (NHLBI)
- National Institute on Drug Abuse (NIDA)
- National Institute of Mental Health (NIMH)
- National Institute of Neurological Disorders and Stroke (NINDS)
- NCISAIC-Frederick, Inc.
- National Disease Research Interchange [10XS170]
- Roswell Park Cancer Institute [10XS171]
- SAIC-F [10ST1035, HHSN261200800001E]
- [HHSN268201000029C]
- [DA006227]
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. Transcriptome-wide mapping of RNAs bound by human ADARs reveals features that determine ADAR binding affinity and editing efficiency.
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