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

By E. Levanon, E. Eisenberg, R. Yelin, S. Nemzer, Martina Hallegger, R. Shemesh, Zipora Y. Fligelman, Avi Shoshan, S. Pollock, Dan Sztybel and 3 more. Nature Biotechnology, 2004

817 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b8ec1358ebe773415b32a6a263ca217cb895a5e3

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In Molecular Biology

Citations in the corpus

ADAR1 Limits RIG-I RNA Detection and Suppresses IFN Production Responding to Viral and Endogenous RNAs (2014, background): “RNA editing occurs in noncoding regions with uncertain biological consequences (12), and the edited RNA molecules constitute the inosine-containing RNA population in the cells (13).”
Widespread A-to-I RNA Editing of Alu-Containing mRNAs in the Human Transcriptome (2004, methodology): “A recent study by Levanon et al. (2004) reported a computational approach for the identification of heavily edited genes in the human transcriptome and found that editing mostly occurs in Alu repeat elements (greater than 92% of the substrates identified), giving us the opportunity to compare the…”
N6-methyl-adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function (2012, background): “It cannot affect the base pairing ability either [17,18].”
Regulating gene expression through RNA nuclear retention. (2005, background): “The NO pathway is induced in cells under various stress conditions, including viral infection and wound healing, as a part of a cellular defense mechanism (reviewed, Lowenstein and Padalko, 2004).”
RADAR: a rigorously annotated database of A-to-I RNA editing (2013, background): “EST database mining also demonstrated that A-to-I editing is quite prevalent in human Alu repeats (13,14).”
Editing modifies the GABAA receptor subunit α3 (2007, methodology): “Bioinformatic techniques have been used to demonstrate abundant hyperediting in Alu sequences within introns and untranslated regions of the human transcriptome (Athanasiadis et al. 2004; Blow et al. 2004; Levanon et al. 2004).”