  RNA editing by members of the double-stranded RNA-specific ADAR family leads
to site-specific conversion of adenosine to inosine (A-to-I) in precursor
messenger RNAs. Editing by ADARs is believed to occur in all metazoa, and is
essential for mammalian development. Currently, only a limited number of human
ADAR substrates are known, while indirect evidence suggests a substantial
fraction of all pre-mRNAs being affected. Here we describe a computational
search for ADAR editing sites in the human transcriptome, using millions of
available expressed sequences. 12,723 A-to-I editing sites were mapped in 1,637
different genes, with an estimated accuracy of 95%, raising the number of known
editing sites by two orders of magnitude. We experimentally validated our
method by verifying the occurrence of editing in 26 novel substrates. A-to-I
editing in humans primarily occurs in non-coding regions of the RNA, typically
in Alu repeats. Analysis of the large set of editing sites indicates the role
of editing in controlling dsRNA stability.
