title: Mammalian conserved ADAR targets comprise only a small fragment of the human editosome.
abstract: BACKGROUND
  ADAR proteins are among the most extensively studied RNA binding proteins. They bind to their target and deaminate specific adenosines to inosines. ADAR activity is essential, and the editing of a subset of their targets is critical for viability. Recently, a huge number of novel ADAR targets were detected by analyzing next generation sequencing data. Most of these novel editing sites are located in lineage-specific genomic repeats, probably a result of overactivity of editing enzymes, thus masking the functional sites. In this study we aim to identify the set of mammalian conserved ADAR targets.
  
  
  RESULTS
  We used RNA sequencing data from human, mouse, rat, cow, opossum, and platypus to define the conserved mammalian set of ADAR targets. We found that the conserved mammalian editing sites are surprisingly small in number and have unique characteristics that distinguish them from non-conserved ones. The sites that constitute the set have a distinct genomic distribution, tend to be located in genes encoding neurotransmitter receptors or other synapse related proteins, and have higher editing and expression levels. We also found a high consistency of editing levels of this set within mice strains and between human and mouse. Tight regulation of editing in these sites across strains and species implies their functional importance.
  
  
  CONCLUSIONS
  Despite the discovery of numerous editing targets, only a small number of them are conserved within mammalian evolution. These sites are extremely highly conserved and exhibit unique features, such as tight regulation, and probably play a pivotal role in mammalian biology.
authors.forename: Yishay
authors.initials: Y
authors.lastname: Pinto
authors.forename: Haim Y
authors.initials: HY
authors.lastname: Cohen
authors.forename: Erez Y
authors.initials: EY
authors.lastname: Levanon
mesh_terms: D000818:Animals; D002417:Cattle; D017124:Conserved Sequence; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D018390:Gene Targeting; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008322:Mammals / Q000235:genetics*; D051379:Mice; D009893:Opossums / Q000235:genetics; D010987:Platypus / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA / Q000379:methods; D015027:Zebrafish / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins