Genome-wide screening for RNA editing sites

Erez Levanon, Compugen Ltd and Tel Aviv University

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. We describe here a computational search for ADAR editing sites in the human transcriptome, using millions of available expressed sequences. 12,220 A-to-I editing sites were mapped in 1,595 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, typically in Alu repeats. Within Alu sequences, specific hotspots for editing were identified. Remarkably, a significant fraction of editing events result in the stabilization of the double-stranded RNA (dsRNA) structure, while only 3% have a neutral effect on pairing. We will describe also the results from cross-genomic search for RNA editing sites and its implications.

Joint work with Eli Eisenberg and others