Evolutionarily conserved human targets of adenosine to inosine RNA editing.
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.
Levanon
Erez Y
EY
Compugen Ltd 72 Pinchas Rosen St, Tel-Aviv 69512, Israel. erez@compugen.co.il
Hallegger
Martina
M
Kinar
Yaron
Y
Shemesh
Ronen
R
Djinovic-Carugo
Kristina
K
Rechavi
Gideon
G
Jantsch
Michael F
MF
Eisenberg
Eli
E
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
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
FEBS Lett. 2004 Jul 2;569(1-3):185-90
15225631
Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1155-7
15159586
Development. 2004 Aug;131(16):3981-9
15269173
Genome Res. 2004 Sep;14(9):1719-25
15342557
J Mol Biol. 2004 Oct 1;342(5):1637-46
15364587
Nat Struct Mol Biol. 2004 Oct;11(10):950-6
15361858
J Biol Chem. 1975 Jul 25;250(14):5696-705
124734
Cell. 1991 Oct 4;67(1):11-9
1717158
Biochemistry. 1991 Dec 10;30(49):11507-14
1747369
Nat Genet. 1993 Aug;4(4):332-3
8401577
Cell. 1993 Dec 31;75(7):1361-70
8269514
Mol Cell Biol. 1995 Oct;15(10):5376-88
7565688
Science. 1995 Dec 8;270(5242):1677-80
7502080
J Biol Chem. 1996 Nov 29;271(48):30322-5
8939990
Nature. 1997 May 15;387(6630):303-8
9153397
Nat Struct Biol. 1997 Mar;4(3):223-30
9164464
Brain Res Brain Res Rev. 1998 May;26(2-3):217-29
9651532
EMBO J. 1998 Nov 16;17(22):6558-72
9822601
Neuron. 1998 Dec;21(6):1315-25
9883725
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2122-8
10051605
EMBO J. 1999 Aug 16;18(16):4424-37
10449408
Nat Struct Biol. 1999 Sep;6(9):836-41
10467095
Genome Res. 2004 Dec;14(12):2379-87
15545495
PLoS Biol. 2004 Dec;2(12):e391
15534692
Nature. 2000 Jul 6;406(6791):78-81
10894545
Cell. 2000 Aug 18;102(4):437-49
10966106
Science. 2000 Dec 1;290(5497):1765-8
11099415
Biochim Biophys Acta. 2001 Apr 23;1538(2-3):99-117
11336782
EMBO J. 2001 Jul 16;20(14):3638-44
11447105
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8844-9
11438699
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14687-92
11717408
Proteins. 2001;Suppl 5:39-46
11835480
Int J Cancer. 2002 Apr 1;98(4):539-46
11920613
Neuron. 2002 Apr 25;34(3):349-56
11988167
Annu Rev Biochem. 2002;71:817-46
12045112
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7906-11
12048240
Genome Res. 2002 Jul;12(7):1060-7
12097342
Bioinformatics. 2002 Aug;18(8):1141-2
12176841
RNA. 2003 Mar;9(3):309-18
12592005
RNA. 2003 Jun;9(6):698-710
12756328
Neuron. 2003 Jun 19;38(6):887-98
12818175
Nucleic Acids Res. 2003 Jul 1;31(13):3381-5
12824332
Nucleic Acids Res. 2003 Jul 1;31(13):3406-15
12824337
Science. 2003 Aug 8;301(5634):832-6
12907802
J Biol Chem. 2004 Feb 6;279(6):4952-61
14613934
J Biol Chem. 2004 Feb 6;279(6):4894-902
14615479
Nature. 2004 Feb 26;427(6977):801
14985749
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7
15075390
Nat Biotechnol. 2004 Aug;22(8):1001-5
15258596