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Nat Biotechnol. 2004 Aug;22(8):1001-5. Epub 2004 Jul 18.

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

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  • 1Compugen Ltd., 72 Pinchas Rosen St., Tel-Aviv 69512, Israel. erez@compugen.co.il

Abstract

RNA editing by members of the ADAR (adenosine deaminases acting on RNA) 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, whereas 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. We mapped 12,723 A-to-I editing sites 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 noncoding 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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PMID:
15258596
[PubMed - indexed for MEDLINE]
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