Genome-wide evaluation and discovery of vertebrate A-to-I RNA editing sites

RNA editing by adenosine deamination, catalyzed by adenosine deaminases acting on RNA (ADAR), is a post-transcriptional modification that contributes to transcriptome and proteome diversity and is widespread in mammals. Here we administer a bioinformatics search strategy to the human and mouse genomes to explore the landscape of A-to-I RNA editing. In both organisms we find evidence for high excess of A/G-type discrepancies (inosine appears as a guanosine in cloned cDNA) at non-polymorphic, non-synonymous codon sites over other types of discrepancies, suggesting the existence of several thousand recoding editing sites in the human and mouse genomes. We experimentally validate recoding-type A-to-I RNA editing in a number of human genes with high scoring positions including the coatomer protein complex subunit alpha (COPA) as well as cyclin dependent kinase CDK13.

► We employ a computational pipeline to predict A-to-I RNA editing recoding sites.
► We reveal high excess of A/G-discrepancies affecting non-synonymous codon sites.
► Most recoding RNA editing events are likely subject to a low level of modification.
► We validate novel recoding events in several human genes including COPA and CDK13.