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

An unbiased genome-wide approach was used to identify 239 sites (in 207 target genes), with stringent criteria for editing, which included 10 of the 13 known edited genes and suggested that many more human genes may be edited at lower frequencies.

Abstract

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 more than 36,000 computationally predicted nonrepetitive A-to-I sites using massively parallel target capture and DNA sequencing. A comprehensive set of several hundred human RNA editing sites was 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 targets of adenosine deaminases acting on RNA (ADAR) and validation by means of capillary sequencing. This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing-related human diseases.