Abstract
ADAR1-mediated deamination of adenosines in long double-stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2-infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments of infected human cell lines and transcriptome data from Vero cells and clinical samples, we prove that A-to-G changes observed in SARS-COV-2 genomes represent genuine RNA editing events, likely mediated by ADAR1. While the A-to-I editing rate is generally low, changes are distributed along the entire viral genome, are overrepresented in exonic regions, and are (in the majority of cases) nonsynonymous. The impact of RNA editing on virus–host interactions could be relevant to identify potential targets for therapeutic interventions.
Highlights
SARS-COV-2 is an enveloped virus with a positive sense, single-stranded RNA genome of about 30 kb belonging to the genus betacoronavirus [1], sadly known for causing the pandemic by coronavirus disease 19 (COVID-19) [2]
The non-random occurrence of this mismatch strongly suggests that the SARS-COV-2 genome could undergo C-to-U RNA editing through APOBECs, as shown in metagenomic experiments from bronchoalveolar lavage fluids (BALF) of COVID-19 patients [4]
We prove that A-to-G changes observed in the SARS-COV-2 genome are genuine RNA editing events likely mediated by ADAR1
Summary
SARS-COV-2 is an enveloped virus with a positive sense, single-stranded RNA (ssRNA) genome of about 30 kb belonging to the genus betacoronavirus [1], sadly known for causing the pandemic by coronavirus disease 19 (COVID-19) [2]. The non-random occurrence of this mismatch strongly suggests that the SARS-COV-2 genome could undergo C-to-U RNA editing through APOBECs, as shown in metagenomic experiments from bronchoalveolar lavage fluids (BALF) of COVID-19 patients [4]. There are contrasting evidences on the occurrence of A-to-I RNA editing [4,5], even though the A-to-G change appears the second most common mismatch type [3] and a recent study based on 62,000 viral isolate sequences (from human infections in the USA) ranks A-to-G (and T-to-C) changes third among all detected mutations [6]. While ADAR2 tends to edit As in coding protein sequences, and has only been detected in a few instances up to now [11], ADAR1 extensively deaminates As in long dsRNAs and exists in two different isoforms: ADAR1p110, constitutively expressed, and ADAR1p150, mainly located in the cytoplasm and inducible by type-I interferon [8]
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