RESIC: A Tool for Comprehensive Adenosine to Inosine RNA Editing Site Identification and Classification

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.

Elevated A-to-I RNA editing in COVID-19 infected individuals

“…Another research was performed by Light and Haas et al. ( 56 ), who reported significant upregulation of all ADAR1 isoforms in SARS-CoV-2 human adenocarcinomic lung epithelial and alveolar basal epithelial infected cells. Using their experimental tool for detecting A-to-I RNA editing, they were able to show that non-repetitive hyper editing sites were much more abundant in SARS-CoV-2 infected cells compared to mock.…”

Harnessing ADAR-Mediated Site-Specific RNA Editing in Immune-Related Disease: Prediction and Therapeutic Implications

“…Other tools design specific mapping schemes for repetitive genomic regions to increase the accuracy of RES detection [ 170 ]. Some tools primarily focus on hyper-editing sites to further characterize RESs that cannot be detected from the typical mutation detection method [ 171 , 172 ]. These tools use unmapped reads to call clusters with hyper-editing via the global A-G mask with a series of filtrations.…”

RNA editing in host lncRNAs as potential modulator in SARS-CoV-2 variants-host immune response dynamics

“… 24 The RNA editing events in the host may be essential for regulating the immune response leading to host defense since there is indirect evidence of pathogen induced upregulation of RNA editors and increased editing sites during an infection. 25 , 26 The diverse effects of RNA editing include alteration of protein coding sequences by incorporation of start/stop codons, alteration of alternative splicing by modifying the splice sites, change in secondary structure, stability, and expression of both mRNAs and lncRNAs. 2 Although lncRNAs possess a higher abundance of repeat elements and dynamic secondary structures, making them ideal candidates for RNA editing, there is limited information available regarding RNA editing in the lncRNAs.…”