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Reduced A-to-I editing of endogenous Alu RNAs in severe COVID-19 disease

ABSTRACT: Severe COVID-19 disease is associated with elevated inflammatory responses. One form of Aicardi-Goutières Syndrome caused by inactivating mutations in ADAR results in reduced A-to-I editing of endogenous double-stranded RNAs (dsRNAs), induction of IFNs, interferon-stimulated genes (ISGs), other inflammatory mediators, morbidity and mortality. Alu elements, ~10% of the human genome, are the most common A-to-I editing sites. Using leukocyte whole-genome RNA sequencing data, we find reduced A-to-I editing of Alu dsRNAs in patients with severe COVID-19 disease. Unedited Alu dsRNAs, but not edited Alu dsRNAs, are potent inducers of IRF and NF-kB transcriptional responses, IL6, IL8 and ISGs. Thus, decreased A-to-I editing that may lead to accumulation of unedited Alu dsRNAs and increased inflammatory responses, is associated with severe COVID-19 disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168286 | GEO | 2021/03/05

REPOSITORIES: GEO

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