{"doi":"10.1101/gr.164749.113","title":"A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes","abstract":"<jats:p>\n                    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\n                    <jats:italic>Alu</jats:italic>\n                    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\n                    <jats:italic>Alu</jats:italic>\n                    sequences and showed that the scope of editing is much larger than anticipated. We found that virtually all adenosines within\n                    <jats:italic>Alu</jats:italic>\n                    repeats that form double-stranded RNA undergo A-to-I editing, although most sites exhibit editing at only low levels (&lt;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\n                    <jats:italic>Alu</jats:italic>\n                    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.\n                  </jats:p>","journal":"Genome Research","year":2014,"id":669499,"datarank":0.9776506909368414,"base_score":6.517671272912275,"endowment":6.517671272912275,"self_citation_contribution":0.9776506909368414,"citation_network_contribution":0.0,"self_endowment_contribution":0.9776506909368414,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":676,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":25,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1748523,"name":"Ami Haviv","orcid":null,"position":1,"is_corresponding":false},{"id":1748524,"name":"Michal Barak","orcid":null,"position":2,"is_corresponding":false},{"id":1748526,"name":"Jasmine Jacob-Hirsch","orcid":null,"position":3,"is_corresponding":false},{"id":278653,"name":"Patricia Deng","orcid":"0000-0001-9717-4143","position":4,"is_corresponding":false},{"id":604716,"name":"Rui Zhang","orcid":"0000-0003-0310-6030","position":5,"is_corresponding":false},{"id":558654,"name":"Farren J. 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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\n                    <jats:italic>Alu</jats:italic>\n                    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\n                    <jats:italic>Alu</jats:italic>\n                    sequences and showed that the scope of editing is much larger than anticipated. We found that virtually all adenosines within\n                    <jats:italic>Alu</jats:italic>\n                    repeats that form double-stranded RNA undergo A-to-I editing, although most sites exhibit editing at only low levels (&lt;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\n                    <jats:italic>Alu</jats:italic>\n                    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.\n                  </jats:p>","is_dataset_classified":null,"base_score":6.517671272912275,"endowment":6.517671272912275,"datacite_reuse_total":25,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24347612","pmcid":"PMC3941102","openalex_id":"https://openalex.org/W2012800815","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM102484","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"T32 HG000044","title":null},{"funder_name":"European Research Council","grant_id":"311257","title":"Genome, the Edited Version: DNA and RNA Editing of Mammalian Retroelements"},{"funder_name":"European Commission","grant_id":"256593","title":"Identification and screen of RNA Editing in the Human 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