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dc.contributor.authorKong, Xiang Yi
dc.contributor.authorVik, Erik Sebastian
dc.contributor.authorNawaz, Meh Sameen
dc.contributor.authorBerges, Natalia
dc.contributor.authorDahl, Tuva Børresdatter
dc.contributor.authorVågbø, Cathrine
dc.contributor.authorSuganthan, Rajikala
dc.contributor.authorSegers, Filip
dc.contributor.authorHolm, Sverre
dc.contributor.authorQuiles-Jimenez, Ana
dc.contributor.authorGregersen, Ida
dc.contributor.authorFladeby, Cathrine
dc.contributor.authorAukrust, Pål
dc.contributor.authorBjørås, Magnar
dc.contributor.authorKlungland, Arne
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorAlseth, Ingrun
dc.description.abstractEndonuclease V (EndoV) is a conserved inosine-specific ribonuclease with unknown biological function. Here, we present the first mouse model lacking EndoV, which is viable without visible abnormalities. We show that endogenous murine EndoV cleaves inosine-containing RNA in vitro, nevertheless a series of experiments fails to link an in vivo function to processing of such transcripts. As inosine levels and adenosine-to-inosine editing often are dysregulated in hepatocellular carcinoma (HCC), we chemically induced HCC in mice. All mice developed liver cancer, however, EndoV−/− tumors were significantly fewer and smaller than wild type tumors. Opposed to human HCC, adenosine deaminase mRNA expression and site-specific editing were unaltered in our model. Loss of EndoV did not affect editing levels in liver tumors, however mRNA expression of a selection of cancer related genes were reduced. Inosines are also found in certain tRNAs and tRNAs are cleaved during stress to produce signaling entities. tRNA fragmentation was dysregulated in EndoV−/− livers and apparently, inosine-independent. We speculate that the inosine-ribonuclease activity of EndoV is disabled in vivo, but RNA binding allowed to promote stabilization of transcripts or recruitment of proteins to fine-tune gene expression. The EndoV−/− tumor suppressive phenotype calls for related studies in human HCC.en_US
dc.publisherOxford University Pressen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleDeletion of Endonuclease V suppresses chemically induced hepatocellular carcinomaen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalNucleic Acids Researchen_US
dc.description.localcode© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comen_US

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