title: Evolutionarily conserved human targets of adenosine to inosine RNA editing.
abstract: A-to-I RNA editing by ADARs is a post-transcriptional mechanism for expanding the proteomic repertoire. Genetic recoding by editing was so far observed for only a few mammalian RNAs that are predominantly expressed in nervous tissues. However, as these editing targets fail to explain the broad and severe phenotypes of ADAR1 knockout mice, additional targets for editing by ADARs were always expected. Using comparative genomics and expressed sequence analysis, we identified and experimentally verified four additional candidate human substrates for ADAR-mediated editing: FLNA, BLCAP, CYFIP2 and IGFBP7. Additionally, editing of three of these substrates was verified in the mouse while two of them were validated in chicken. Interestingly, none of these substrates encodes a receptor protein but two of them are strongly expressed in the CNS and seem important for proper nervous system function. The editing pattern observed suggests that some of the affected proteins might have altered physiological properties leaving the possibility that they can be related to the phenotypes of ADAR1 knockout mice.
authors.affiliation: Compugen Ltd 72 Pinchas Rosen St, Tel-Aviv 69512, Israel. erez@compugen.co.il
authors.forename: Erez Y
authors.initials: EY
authors.lastname: Levanon
authors.forename: Martina
authors.initials: M
authors.lastname: Hallegger
authors.forename: Yaron
authors.initials: Y
authors.lastname: Kinar
authors.forename: Ronen
authors.initials: R
authors.lastname: Shemesh
authors.forename: Kristina
authors.initials: K
authors.lastname: Djinovic-Carugo
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jantsch
authors.forename: Eli
authors.initials: E
authors.lastname: Eisenberg
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D002645:Chickens / Q000235:genetics; D003285:Contractile Proteins / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D064448:Filamins; D023281:Genomics / Q000379:methods; D006801:Humans; D007288:Inosine / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D017393:RNA Editing; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins
chemical_list: C453739:BLCAP protein, human; D003285:Contractile Proteins; D064448:Filamins; D018969:Insulin-Like Growth Factor Binding Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1; D007288:Inosine; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D000241:Adenosine
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