Abstract
Adenosine to inosine (A-to-I) RNA editing, the most prevalent type of RNA editing in metazoans, is carried out by adenosine deaminases (ADARs) in double-stranded RNA regions. Several computational approaches have been recently developed to identify A-to-I RNA editing sites from sequencing data, each addressing a particular issue. Here, we present RNA Editing Sites Identification and Classification (RESIC), an efficient pipeline that combines several approaches for the detection and classification of RNA editing sites. The pipeline can be used for all organisms and can use any number of RNA-sequencing datasets as input. RESIC provides (1) the detection of editing sites in both repetitive and non-repetitive genomic regions; (2) the identification of hyper-edited regions; and (3) optional exclusion of polymorphism sites to increase reliability, based on DNA, and ADAR-mutant RNA sequencing datasets, or SNP databases. We demonstrate the utility of RESIC by applying it to human, successfully overlapping and extending the list of known putative editing sites. We further tested changes in the patterns of A-to-I RNA editing, and RNA abundance of ADAR enzymes, following SARS-CoV-2 infection in human cell lines. Our results suggest that upon SARS-CoV-2 infection, compared to mock, the number of hyper editing sites is increased, and in agreement, the activity of ADAR1, which catalyzes hyper-editing, is enhanced. These results imply the involvement of A-to-I RNA editing in conceiving the unpredicted phenotype of COVID-19 disease. RESIC code is open-source and is easily extendable.
Highlights
The conversion of adenosine to inosine (A-to-I) in double-stranded RNA regions, by adenosine deaminases (ADARs) enzymes, is the most common form of RNA editing in metazoans (Bazak et al, 2014)
We demonstrate the utility of RNA Editing Sites Identification and Classification (RESIC) by applying it to mapping A-to-I RNA editing sites in 16 human tissues, from the Illumina Human Body Map project, analyzed for a similar purpose by others (Zhu et al, 2013; Bazak et al, 2014; Porath et al, 2014)
The list of obtained editing sites was compared to the entire list from RADAR database (Ramaswami and Li, 2014), We considered as shared editing sites, sites that are included in the RADAR list or sites that have gene annotations similar to the ones appeared in the RADAR list
Summary
The conversion of adenosine to inosine (A-to-I) in double-stranded RNA regions, by adenosine deaminases (ADARs) enzymes, is the most common form of RNA editing in metazoans (Bazak et al, 2014) This type of RNA editing is crucial for normal development of an organism and has a major role in the innate immune response (Mannion et al, 2014; Ganem and Lamm, 2017; Eisenberg and Levanon, 2018). ADARs are known to be involved in regulation of innate immune response by blocking the interferon (IFN) response upon viral infection (Quin et al, 2021) For these reasons, A-to-I RNA editing is an extensively studied research field in many organisms, and identification of editing sites is of major interest
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