title: Endonuclease V cleaves at inosines in RNA.
abstract: Endonuclease V orthologues are highly conserved proteins found in all kingdoms of life. While the prokaryotic enzymes are DNA repair proteins for removal of deaminated adenosine (inosine) from the genome, no clear role for the eukaryotic counterparts has hitherto been described. Here we report that human endonuclease V (ENDOV) and also Escherichia coli endonuclease V are highly active ribonucleases specific for inosine in RNA. Inosines are normal residues in certain RNAs introduced by specific deaminases. Adenosine-to-inosine editing is essential for proper function of these transcripts and defects are linked to various human disease. Here we show that human ENDOV cleaves an RNA substrate containing inosine in a position corresponding to a biologically important site for deamination in the Gabra-3 transcript of the GABA(A) neurotransmitter. Further, human ENDOV specifically incises transfer RNAs with inosine in the wobble position. This previously unknown RNA incision activity may suggest a role for endonuclease V in normal RNA metabolism.
authors.affiliation: Department of Microbiology, Oslo University Hospital HF and University of Oslo, Rikshospitalet, PO Box 4950 Nydalen, 0424 Oslo, Norway.
authors.forename: Erik Sebastian
authors.initials: ES
authors.lastname: Vik
authors.forename: Meh Sameen
authors.initials: MS
authors.lastname: Nawaz
authors.forename: Pernille
authors.initials: P
authors.lastname: Strøm Andersen
authors.forename: Cathrine
authors.initials: C
authors.lastname: Fladeby
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
authors.forename: Bjørn
authors.initials: B
authors.lastname: Dalhus
authors.forename: Ingrun
authors.initials: I
authors.lastname: Alseth
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D007288:Inosine / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D007288:Inosine; D012313:RNA; D004247:DNA; D012343:RNA, Transfer; D043224:Deoxyribonuclease (Pyrimidine Dimer)
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