Home LiteratureArticle Details
PMID: 23912718 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Human endonuclease V is a ribonuclease specific for inosine-containing RNA.

Nature communications ·Vol. 4 ·2013-00-00 ·Pages 2273

Morita Y, Shibutani T, Nakanishi N, Nishikura K, Iwai S, Kuraoka I

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.

MeSH Terms
Adenosine Deaminase/metabolism Amino Acid Sequence Base Sequence Cytoplasm/enzymology DNA/metabolism DNA-Binding Proteins/metabolism Deoxyribonuclease (Pyrimidine Dimer)/metabolism Endonucleases/metabolism HEK293 Cells Humans Inosine/metabolism Molecular Sequence Data Protein Transport RNA, Double-Stranded/metabolism RNA-Binding Proteins/metabolism Recombinant Proteins/metabolism Ribonucleases/metabolism Substrate Specificity
Chemicals
DNA-Binding Proteins RNA, Double-Stranded RNA-Binding Proteins Recombinant Proteins TSN protein, human Inosine DNA Endonucleases Ribonucleases Deoxyribonuclease (Pyrimidine Dimer) ADARB1 protein, human Adenosine Deaminase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Morita Yoko
Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
Shibutani Toshihiro
Nakanishi Nozomi
Nishikura Kazuko
Iwai Shigenori
Kuraoka Isao
References (39)
39 references, click to expand
  1. Functions and regulation of RNA editing by ADAR deaminases.
    Annu Rev Biochem. 2010;79:321-49 PMID: 20192758
  2. Incision at hypoxanthine residues in DNA by a mammalian homologue of the Escherichia coli antimutator enzyme endonuclease V.
    Nucleic Acids Res. 2003 Jul 15;31(14):3893-900 PMID: 12853604
  3. Strand-specific cleavage of mismatch-containing DNA by deoxyinosine 3'-endonuclease from Escherichia coli.
    J Biol Chem. 1994 Dec 16;269(50):31390-6 PMID: 7989304
  4. Endonuclease V-mediated deoxyinosine excision repair in vitro.
    DNA Repair (Amst). 2010 Oct 5;9(10):1073-9 PMID: 20696623
  5. Counteraction by MutT protein of transcriptional errors caused by oxidative damage.
    Science. 1997 Oct 3;278(5335):128-30 PMID: 9311918
  6. Human endonuclease V as a repair enzyme for DNA deamination.
    Mutat Res. 2012 Jul 1;735(1-2):12-8 PMID: 22664237
  7. The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage.
    Nat Struct Mol Biol. 2005 Jun;12(6):489-96 PMID: 15895094
  8. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs.
    Science. 2007 Feb 23;315(5815):1137-40 PMID: 17322061
  9. Increased RNA editing and inhibition of hepatitis delta virus replication by high-level expression of ADAR1 and ADAR2.
    J Virol. 2002 Apr;76(8):3819-27 PMID: 11907222
  10. Editing of glutamate receptor B subunit ion channel RNAs by four alternatively spliced DRADA2 double-stranded RNA adenosine deaminases.
    Mol Cell Biol. 1997 May;17(5):2413-24 PMID: 9111310
  11. Structures of endonuclease V with DNA reveal initiation of deaminated adenine repair.
    Nat Struct Mol Biol. 2009 Feb;16(2):138-43 PMID: 19136958
  12. Endonuclease V protects Escherichia coli against specific mutations caused by nitrous acid.
    Mutat Res. 1999 Dec 7;435(3):245-54 PMID: 10606815
  13. Translesion synthesis by RNA polymerases: occurrence and biological implications for transcriptional mutagenesis.
    Mutat Res. 2002 Dec 29;510(1-2):131-40 PMID: 12459449
  14. Purification and characterization of a novel deoxyinosine-specific enzyme, deoxyinosine 3' endonuclease, from Escherichia coli.
    J Biol Chem. 1994 Jun 10;269(23):16260-8 PMID: 8206931
  15. Modulation of RNA editing by functional nucleolar sequestration of ADAR2.
    Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14018-23 PMID: 14612560
  16. A ribonuclease specific for inosine-containing RNA: a potential role in antiviral defence?
    EMBO J. 1997 Apr 15;16(8):2140-9 PMID: 9155039
  17. A mammalian RNA editing enzyme.
    Nature. 1996 Feb 1;379(6564):460-4 PMID: 8559253
  18. Mutational analysis of endonuclease V from Thermotoga maritima.
    Biochemistry. 2002 Jul 2;41(26):8342-50 PMID: 12081482
  19. Quality control by DNA repair.
    Science. 1999 Dec 3;286(5446):1897-905 PMID: 10583946
  20. Cleavage of insertion/deletion mismatches, flap and pseudo-Y DNA structures by deoxyinosine 3'-endonuclease from Escherichia coli.
    J Biol Chem. 1996 Nov 29;271(48):30672-6 PMID: 8940043
  21. Double-stranded RNA adenosine deaminase ADAR-1-induced hypermutated genomes among inactivated seasonal influenza and live attenuated measles virus vaccines.
    J Virol. 2011 Mar;85(5):2458-62 PMID: 21159878
  22. RNAi is antagonized by A-->I hyper-editing.
    EMBO Rep. 2001 Dec;2(12):1107-11 PMID: 11743024
  23. On the recognition and cleavage mechanism of Escherichia coli endodeoxyribonuclease V, a possible DNA repair enzyme.
    J Biol Chem. 1982 Mar 25;257(6):2848-55 PMID: 6277916
  24. Cleavage of dsRNAs hyper-edited by ADARs occurs at preferred editing sites.
    Nucleic Acids Res. 2005 Oct 27;33(18):5954-64 PMID: 16254076
  25. Inosine exists in mRNA at tissue-specific levels and is most abundant in brain mRNA.
    EMBO J. 1998 Feb 16;17(4):1120-7 PMID: 9463389
  26. Pin1 and WWP2 regulate GluR2 Q/R site RNA editing by ADAR2 with opposing effects.
    EMBO J. 2011 Aug 16;30(20):4211-22 PMID: 21847096
  27. NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest.
    Nucleic Acids Res. 2010 Aug;38(14):4834-43 PMID: 20385596
  28. The human homolog of Escherichia coli endonuclease V is a nucleolar protein with affinity for branched DNA structures.
    PLoS One. 2012;7(11):e47466 PMID: 23139746
  29. Cloning and characterization of a 3-methyladenine DNA glycosylase cDNA from human cells whose gene maps to chromosome 16.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9127-31 PMID: 1924375
  30. Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA.
    Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2319-24 PMID: 22308425
  31. Dynamic association of RNA-editing enzymes with the nucleolus.
    J Cell Sci. 2003 May 1;116(Pt 9):1805-18 PMID: 12665561
  32. Endonuclease V of Escherichia coli prevents mutations from nitrosative deamination during nitrate/nitrite respiration.
    Mutat Res. 2001 Jan 5;461(4):301-9 PMID: 11104906
  33. Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein.
    EMBO J. 1996 Dec 2;15(23):6662-70 PMID: 8978692
  34. RNA-regulated interaction of transportin-1 and exportin-5 with the double-stranded RNA-binding domain regulates nucleocytoplasmic shuttling of ADAR1.
    Mol Cell Biol. 2009 Mar;29(6):1487-97 PMID: 19124606
  35. Deoxyxanthosine in DNA is repaired by Escherichia coli endonuclease V.
    Mutat Res. 2000 Mar 20;459(2):109-14 PMID: 10725661
  36. Base excision and DNA binding activities of human alkyladenine DNA glycosylase are sensitive to the base paired with a lesion.
    J Biol Chem. 2001 Apr 20;276(16):13379-87 PMID: 11278716
  37. ADAR1 RNA deaminase limits short interfering RNA efficacy in mammalian cells.
    J Biol Chem. 2005 Feb 4;280(5):3946-53 PMID: 15556947
  38. RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase.
    Nature. 1996 Apr 4;380(6573):454-6 PMID: 8602246
  39. Instability and decay of the primary structure of DNA.
    Nature. 1993 Apr 22;362(6422):709-15 PMID: 8469282
Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms3273
Published
2013-00-00
Pages
2273
Language
English
Region
England
NLM ID
101528555
PMCID
PMC3741642
Subset
IM
Grants
NIGMS NIH HHS · GM040536 · United States
NIGMS NIH HHS · R01 GM040536 · United States
NHLBI NIH HHS · R01 HL070045 · United States
NHLBI NIH HHS · HL099342 · United States
NHLBI NIH HHS · HL070045 · United States
NHLBI NIH HHS · RC1 HL099342 · United States
External Links
PubMed source DOI: 10.1038/ncomms3273 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2