RT Journal
A1 Bazak, Lily
A1 Haviv, Ami
A1 Barak, Michal
A1 Jacob-Hirsch, Jasmine
A1 Deng, Patricia
A1 Zhang, Rui
A1 Isaacs, Farren J.
A1 Rechavi, Gideon
A1 Li, Jin Billy
A1 Eisenberg, Eli
A1 Levanon, Erez Y.
T1 A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes
JF Genome Research 
JO Genome Research 
YR 2014 
FD March 01 
VO 24 
IS 3 
SP 365 
OP 376 
DO 10.1101/gr.164749.113 
UL http://genome.cshlp.org/content/24/3/365.abstract 
AB RNA molecules transmit the information encoded in the genome and generally reflect its content. Adenosine-to-inosine (A-to-I) RNA editing by ADAR proteins converts a genomically encoded adenosine into inosine. It is known that most RNA editing in human takes place in the primate-specific Alu sequences, but the extent of this phenomenon and its effect on transcriptome diversity are not yet clear. Here, we analyzed large-scale RNA-seq data and detected ∼1.6 million editing sites. As detection sensitivity increases with sequencing coverage, we performed ultradeep sequencing of selected Alu sequences and showed that the scope of editing is much larger than anticipated. We found that virtually all adenosines within Alu repeats that form double-stranded RNA undergo A-to-I editing, although most sites exhibit editing at only low levels (<1%). Moreover, using high coverage sequencing, we observed editing of transcripts resulting from residual antisense expression, doubling the number of edited sites in the human genome. Based on bioinformatic analyses and deep targeted sequencing, we estimate that there are over 100 million human Alu RNA editing sites, located in the majority of human genes. These findings set the stage for exploring how this primate-specific massive diversification of the transcriptome is utilized.