Systematic identification of abundant A-to-I editing sites in the human transcriptome.
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.
Levanon
Erez Y
EY
Compugen Ltd., 72 Pinchas Rosen St., Tel-Aviv 69512, Israel. erez@compugen.co.il
Eisenberg
Eli
E
Yelin
Rodrigo
R
Nemzer
Sergey
S
Hallegger
Martina
M
Shemesh
Ronen
R
Fligelman
Zipora Y
ZY
Shoshan
Avi
A
Pollock
Sarah R
SR
Sztybel
Dan
D
Olshansky
Moshe
M
Rechavi
Gideon
G
Jantsch
Michael F
MF
D000241:Adenosine / Q000235:genetics*; D020137:Base Pair Mismatch / Q000235:genetics; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D020224:Expressed Sequence Tags; D006801:Humans; D007288:Inosine / Q000235:genetics*; D008969:Molecular Sequence Data; D017393:RNA Editing / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*
D014157:Transcription Factors; D007288:Inosine; D000241:Adenosine