Abstract
SARS-CoV-2 is a positive-sense, single-stranded RNA virus responsible for the COVID-19 pandemic. It remains unclear whether and to what extent the virus in human host cells undergoes RNA editing, a major RNA modification mechanism. Here we perform a robust bioinformatic analysis of metatranscriptomic data from multiple bronchoalveolar lavage fluid samples of COVID-19 patients, revealing an appreciable number of A-to-I RNA editing candidate sites in SARS-CoV-2. We confirm the enrichment of A-to-I RNA editing signals at these candidate sites through evaluating four characteristics specific to RNA editing: the inferred RNA editing sites exhibit (i) stronger ADAR1 binding affinity predicted by a deep-learning model built from ADAR1 CLIP-seq data, (ii) decreased editing levels in ADAR1-inhibited human lung cells, (iii) local clustering patterns, and (iv) higher RNA secondary structure propensity. Our results have critical implications in understanding the evolution of SARS-CoV-2 as well as in COVID-19 research, such as phylogenetic analysis and vaccine development.
【초록키워드】 RNA modification, SARS-CoV-2, Vaccine development, COVID-19 pandemic, Local, virus, binding affinity, RNA, Phylogenetic analysis, Characteristics, Bronchoalveolar lavage fluid, Clustering, Evolution of SARS-CoV-2, RNA secondary structure, RNA virus, Critical, mechanism, COVID-19 patients, secondary structure, enrichment, human lung cells, single-stranded RNA virus, COVID-19 research, bioinformatic analysis, human host cells, implication, positive-sense, robust, responsible, predicted, human host cell, metatranscriptomic, 【제목키워드】 SARS-CoV-2, RNA, nucleotide, increase, human host cell,