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A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes

2013; Cold Spring Harbor Laboratory Press; Volume: 24; Issue: 3 Linguagem: Inglês

10.1101/gr.164749.113

1549-5469

Lily Bazak, Ami Haviv, Michal Barák, Jasmine Jacob‐Hirsch, Patricia Deng, Rui Zhang, Farren J. Isaacs, Gideon Rechavi, Jin Billy Li, Eli Eisenberg, Erez Y. Levanon,

RNA modifications and cancer

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.