Systematic identification of abundant A-to-I editing sites in the human transcriptome

Details Systematic identification of abundant A-to-I editing sites in the human transcriptome Systematic identification of abundant A-to-I editing sites in the human transcriptome

2004-11-25

arxiv.org/abs/q-bio/0411045v1

Nature Biotechnology 22, 1001-1005 (2004)

Biology

Quantitative Biology

Genomics

Pre-print version. See http://dx.doi.org/10.1038/nbt996 for a reprint

Scientific paper

10.1038/nbt996

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.

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