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

Erez Y. Levanon, Eli Eisenberg, Rodrigo Yelin, Sergey Nemzer, Martina Hallegger, Ronen Shemesh, Zipora Y. Fligelman, Avi Shoshan, Sarah R. Pollock, Dan Sztybel, Moshe Olshansky, Gideon Rechavi, Michael F. Jantsch

Research output: Contribution to journalArticleResearchpeer-review

559 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1001-1005
Number of pages5
JournalNature Biotechnology
Volume22
Issue number8
DOIs
Publication statusPublished - 1 Aug 2004

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