Genome analysis A bioinformatic screen for novel A–I RNA editing sites reveals recoding editing in BC10

Motivation: Recent studies have demonstrated widespread adenosine–inosine RNA editing in non-coding sequence. However, the extent of editing in coding sequences has remained unknown. For many of the known sites, editing can be observed in multiple spe-cies and often occurs in well-conserved sequences. In addition, they often occur within imperfect inverted repeats and in clusters. Here we present a bioinformatic approach to identify novel sites based on these shared features. Mismatches between genomic and expressed sequences were filtered to remove the main sources of false posit-ives, and then prioritized based on these features. This protocol is tailored to identifying specific recoding editing sites, rather than sites in non-coding repeat sequences. Results: Our protocol is more sensitive for identifying known cod-ing editing sites than any previously published mammalian screen. A novel multiply edited transcript, BC10, was identified and experimen-tally verified. BC10 is highly conserved across a range of metazoa and has been implicated in two forms of cancer. Contact