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

• Published in: Biochemical and biophysical research communications Vol. 412; no. 3; pp. 407 - 412
• Main Authors: Maas, S., Godfried Sie, C.P., Stoev, I., Dupuis, D.E., Latona, J., Porman, A.M., Evans, B., Rekawek, P., Kluempers, V., Mutter, M., Gommans, W.M., Lopresti, D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.09.2011
• Subjects: ADAR; Adenine - metabolism; adenosine; Adenosine deamination; Animals; Base Sequence; bioinformatics; complementary DNA; deamination; genes; Genome, Human; Genomics; guanosine; Humans; Inosine; Inosine - metabolism; landscapes; Mice; proteome; RNA; RNA editing; RNA Editing - genetics; Transcriptome; Adenosine deamination; Inosine; RNA editing; ADAR
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2011.07.075

► 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. 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.