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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
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Abstract

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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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. 2004-11-25. Systematic identification of abundant A-to-I editing sites in the human transcriptome. https://doi.org/10.1038/nbt996

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