title: Human endonuclease V is a ribonuclease specific for inosine-containing RNA.
abstract: Deamination of DNA bases can create missense mutations predisposing humans to cancer and also interfere with other basic molecular genetic processes; this deamination generates deoxyinosine from deoxyadenosine. In Escherichia coli, the highly conserved endonuclease V is involved in alternative excision repair that removes deoxyinosine from DNA. However, its exact activities and roles in humans are unknown. Here we characterize the FLJ35220 protein, the human homologue of E. coli endonuclease V, hEndoV as a ribonuclease specific for inosine-containing RNA. hEndoV preferentially binds to RNA and efficiently hydrolyses the second phosphodiester bond located 3' to the inosine in unpaired inosine-containing ssRNA regions in dsRNA. It localizes to the cytoplasm in cells. The ribonuclease activity is promoted by Tudor staphylococcal nuclease and detected on inosine-containing dsRNA created by the action of adenosine deaminases acting on RNA. These results demonstrate that hEndoV controls the fate of inosine-containing RNA in humans.
authors.affiliation: Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Morita
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shibutani
authors.forename: Nozomi
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nishikura
authors.forename: Shigenori
authors.initials: S
authors.lastname: Iwai
authors.forename: Isao
authors.initials: I
authors.lastname: Kuraoka
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D003593:Cytoplasm / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007288:Inosine / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport; D012330:RNA, Double-Stranded / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D004268:DNA-Binding Proteins; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C095563:TSN protein, human; D007288:Inosine; D004247:DNA; D004720:Endonucleases; D012260:Ribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C567955:ADARB1 protein, human; D000243:Adenosine Deaminase
references.citation: Annu Rev Biochem. 2010;79:321-49
references.pmid: 20192758
references.citation: Nucleic Acids Res. 2003 Jul 15;31(14):3893-900
references.pmid: 12853604
references.citation: J Biol Chem. 1994 Dec 16;269(50):31390-6
references.pmid: 7989304
references.citation: DNA Repair (Amst). 2010 Oct 5;9(10):1073-9
references.pmid: 20696623
references.citation: Science. 1997 Oct 3;278(5335):128-30
references.pmid: 9311918
references.citation: Mutat Res. 2012 Jul 1;735(1-2):12-8
references.pmid: 22664237
references.citation: Nat Struct Mol Biol. 2005 Jun;12(6):489-96
references.pmid: 15895094
references.citation: Science. 2007 Feb 23;315(5815):1137-40
references.pmid: 17322061
references.citation: J Virol. 2002 Apr;76(8):3819-27
references.pmid: 11907222
references.citation: Mol Cell Biol. 1997 May;17(5):2413-24
references.pmid: 9111310
references.citation: Nat Struct Mol Biol. 2009 Feb;16(2):138-43
references.pmid: 19136958
references.citation: Mutat Res. 1999 Dec 7;435(3):245-54
references.pmid: 10606815
references.citation: Mutat Res. 2002 Dec 29;510(1-2):131-40
references.pmid: 12459449
references.citation: J Biol Chem. 1994 Jun 10;269(23):16260-8
references.pmid: 8206931
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14018-23
references.pmid: 14612560
references.citation: EMBO J. 1997 Apr 15;16(8):2140-9
references.pmid: 9155039
references.citation: Nature. 1996 Feb 1;379(6564):460-4
references.pmid: 8559253
references.citation: Biochemistry. 2002 Jul 2;41(26):8342-50
references.pmid: 12081482
references.citation: Science. 1999 Dec 3;286(5446):1897-905
references.pmid: 10583946
references.citation: J Biol Chem. 1996 Nov 29;271(48):30672-6
references.pmid: 8940043
references.citation: J Virol. 2011 Mar;85(5):2458-62
references.pmid: 21159878
references.citation: EMBO Rep. 2001 Dec;2(12):1107-11
references.pmid: 11743024
references.citation: J Biol Chem. 1982 Mar 25;257(6):2848-55
references.pmid: 6277916
references.citation: Nucleic Acids Res. 2005 Oct 27;33(18):5954-64
references.pmid: 16254076
references.citation: EMBO J. 1998 Feb 16;17(4):1120-7
references.pmid: 9463389
references.citation: EMBO J. 2011 Aug 16;30(20):4211-22
references.pmid: 21847096
references.citation: Nucleic Acids Res. 2010 Aug;38(14):4834-43
references.pmid: 20385596
references.citation: PLoS One. 2012;7(11):e47466
references.pmid: 23139746
references.citation: Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9127-31
references.pmid: 1924375
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2319-24
references.pmid: 22308425
references.citation: J Cell Sci. 2003 May 1;116(Pt 9):1805-18
references.pmid: 12665561
references.citation: Mutat Res. 2001 Jan 5;461(4):301-9
references.pmid: 11104906
references.citation: EMBO J. 1996 Dec 2;15(23):6662-70
references.pmid: 8978692
references.citation: Mol Cell Biol. 2009 Mar;29(6):1487-97
references.pmid: 19124606
references.citation: Mutat Res. 2000 Mar 20;459(2):109-14
references.pmid: 10725661
references.citation: J Biol Chem. 2001 Apr 20;276(16):13379-87
references.pmid: 11278716
references.citation: J Biol Chem. 2005 Feb 4;280(5):3946-53
references.pmid: 15556947
references.citation: Nature. 1996 Apr 4;380(6573):454-6
references.pmid: 8602246
references.citation: Nature. 1993 Apr 22;362(6422):709-15
references.pmid: 8469282