TY  - JOUR
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
Y1  - 2014/03/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 365 
EP  - 376 
DO  - 10.1101/gr.164749.113 
VL  - 24 
IS  - 3 
UR  - http://genome.cshlp.org/content/24/3/365.abstract 
N2  - 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. 
ER  -