Key result
ADAR-mediated A-to-I RNA editing occurs in SARS-CoV-2, averaging 91 events per sample, and introduces recoding mutations in the spike protein that may fuel viral evolution.
Why the study?
Upon SARS-CoV-2 infection, viral intermediates activate the Type I IFN response and induce ADAR1 p150 expression, which might lead to A-to-I RNA editing of SARS-CoV-2.
Observational (n=7,622)
May contribute to SARS-CoV-2 variant emergence; leaves open ADAR editing's role in driving ongoing evolution.
Upon SARS-CoV-2 infection, viral intermediates activate the Type I interferon (IFN) response through MDA5-mediated sensing and accordingly induce ADAR1 p150 expression, which might lead to A-to-I RNA editing of SARS-CoV-2. Here, we developed an RNA virus-specific editing identification pipeline, surveyed 7622 RNA-seq data from diverse types of samples infected with SARS-CoV-2, and constructed an atlas of A-to-I RNA editing sites in SARS-CoV-2. We found that A-to-I editing was dynamically regulated, and on average, approximately 91 editing events were deposited at viral dsRNA intermediates per sample. Moreover, editing hotspots were observed, including recoding sites in the spike gene that affect viral infectivity and antigenicity. Finally, we provided evidence that RNA editing accelerated SARS-CoV-2 evolution in humans. Collectively, our data suggest that SARS-CoV-2 hijacks components of the host antiviral machinery to edit its genome and fuel its evolution.
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Song et al. (2021) conducted an observational in SARS-CoV-2 infection (n=7,622). A-to-I RNA editing vs. Unedited viral sequences was evaluated on Identification and frequency of A-to-I RNA editing events in the SARS-CoV-2 genome. ADAR-mediated A-to-I RNA editing occurs in SARS-CoV-2, averaging 91 events per sample, and introduces recoding mutations in the spike protein that may fuel viral evolution.
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