| First Author | Kong XY | Year | 2020 |
| Journal | Nucleic Acids Res | Volume | 48 |
| Issue | 8 | Pages | 4463-4479 |
| PubMed ID | 32083667 | Mgi Jnum | J:293118 |
| Mgi Id | MGI:6451274 | Doi | 10.1093/nar/gkaa115 |
| Citation | Kong XY, et al. (2020) Deletion of Endonuclease V suppresses chemically induced hepatocellular carcinoma. Nucleic Acids Res 48(8):4463-4479 |
| abstractText | Endonuclease 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. |
