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

Nature Biotechnology volume 22, pages 1001–1005 (2004)Cite this article

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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Figure 1: ADAR-mediated editing.
Figure 2: Distribution of mismatches between the DNA and the expressed RNA sequences that pass the cleaning algorithm.
Figure 3: Editing in the CFLAR transcript.
Figure 4: Editing in the F11 receptor (JAM1) gene.

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Acknowledgements

We thank A. Diber, E. Shuster and S. Zevin for technical help and P. Akiva, A. Amit and R. Sorek for critical reading of the manuscript. The work of E.Y.L. was done in partial fulfillment of the requirements for a PhD degree from the Sackler Faculty of Medicine, Tel Aviv University, Israel. Part of this work was supported by the Austrian Science Foundation grant SFB1706 to M.J.

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Author notes

  1. Erez Y Levanon, Eli Eisenberg, Rodrigo Yelin and Sergey Nemzer: These authors contributed equally to this work.

Authors and Affiliations

  1. Compugen Ltd., 72 Pinchas Rosen St., Tel-Aviv, 69512, Israel

    Erez Y Levanon, Eli Eisenberg, Rodrigo Yelin, Sergey Nemzer, Ronen Shemesh, Zipora Y Fligelman, Avi Shoshan, Sarah R Pollock, Dan Sztybel & Moshe Olshansky

  2. Department of Pediatric Hematology-Oncology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, 52621, Israel

    Erez Y Levanon & Gideon Rechavi

  3. Max F. Perutz Laboratories, Dept. of Cell Biology and Genetics, University of Vienna, Rennweg 14, Vienna, A-1030, Austria

    Martina Hallegger & Michael F Jantsch

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Correspondence to Erez Y Levanon.

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Some authors are past or present employees of Compugen, Ltd.

Supplementary information

Supplementary Fig. 1

Editing in the predicted MGC3329 transcript. (PDF 310 kb)

Supplementary Notes (PDF 32 kb)

Supplementary Methods (PDF 39 kb)

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Levanon, E., Eisenberg, E., Yelin, R. et al. Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat Biotechnol 22, 1001–1005 (2004). https://doi.org/10.1038/nbt996

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