Genome-wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing

Adenosine-to-Inosine (A-to-I) RNA editing leads to transcriptome diversity and is important for normal brain function. To date, only a handful of functional sites have been identified in mammals. We developed an unbiased assay to screen >36,000 computationally predicted non-repetitive A-to-I sites, utilizing massively parallel target capture and DNA sequencing. The first comprehensive set of hundreds of human RNA editing sites were detected by comparing genomic DNA with RNAs from seven tissues of a single individual. Specificity of our profiling was supported by observations of enrichment with known features of ADAR targets and validation by capillary sequencing. Many sites are unique to the primate lineage. This expended repertoire of editing substrates will provide additional targets for understanding the role that RNA editing plays in normal brain function.