title: Complex regulation of ADAR-mediated RNA-editing across tissues.
abstract: BACKGROUND
  RNA-editing is a tightly regulated, and essential cellular process for a properly functioning brain. Dysfunction of A-to-I RNA editing can have catastrophic effects, particularly in the central nervous system. Thus, understanding how the process of RNA-editing is regulated has important implications for human health. However, at present, very little is known about the regulation of editing across tissues, and individuals.
  
  
  RESULTS
  Here we present an analysis of RNA-editing patterns from 9 different tissues harvested from a single mouse. For comparison, we also analyzed data for 5 of these tissues harvested from 15 additional animals. We find that tissue specificity of editing largely reflects differential expression of substrate transcripts across tissues. We identified a surprising enrichment of editing in intronic regions of brain transcripts, that could account for previously reported higher levels of editing in brain. There exists a small but remarkable amount of editing which is tissue-specific, despite comparable expression levels of the edit site across multiple tissues. Expression levels of editing enzymes and their isoforms can explain some, but not all of this variation.
  
  
  CONCLUSIONS
  Together, these data suggest a complex regulation of the RNA-editing process beyond transcript expression levels.
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, USA. huntley.melanie@gene.com.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Huntley
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, USA. melanie.jj.lou@gmail.com.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lou
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, USA. goldstein.leonard@gene.com.
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Goldstein
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, USA. lawrence.michael@gene.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Lawrence
authors.affiliation: Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, USA. dijkgraaf.peter@gene.com.
authors.forename: Gerrit J P
authors.initials: GJ
authors.lastname: Dijkgraaf
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, USA. kaminker.josh@gene.com.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Kaminker
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, USA. rgentlem@gmail.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Gentleman
mesh_terms: D000243:Adenosine Deaminase / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D009928:Organ Specificity / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D020033:Protein Isoforms; D016601:RNA-Binding Proteins; C000599465:ADAR1 protein, mouse; C000595151:ADAR2 protein, mouse; D000243:Adenosine Deaminase