Title | Ribonuclease L mediates the cell-lethal phenotype of double-stranded RNA editing enzyme ADAR1 deficiency in a human cell line. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Li, Y, Banerjee, S, Goldstein, SA, Dong, B, Gaughan, C, Rath, S, Donovan, J, Korennykh, A, Silverman, RH, Weiss, SR |
Journal | Elife |
Volume | 6 |
Date Published | 2017 03 31 |
ISSN | 2050-084X |
Keywords | Adaptor Proteins, Signal Transducing, Adenosine Deaminase, Cell Death, Cell Line, Tumor, Endoribonucleases, Epithelial Cells, Humans, Interferon-Induced Helicase, IFIH1, RNA-Binding Proteins |
Abstract | <p>ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of leads to a severe neurodevelopmental and inflammatory disease of children, Aicardi-Goutiéres syndrome. In mice, mutations are embryonic lethal but are rescued by mutation of the or genes, which function in IFN induction. However, the specific IFN regulated proteins responsible for the pathogenic effects of mutation are unknown. We show that the cell-lethal phenotype of deletion in human lung adenocarcinoma A549 cells is rescued by CRISPR/Cas9 mutagenesis of the gene or by expression of the RNase L antagonist, murine coronavirus NS2 accessory protein. Our result demonstrate that ablation of RNase L activity promotes survival of ADAR1 deficient cells even in the presence of MDA5 and MAVS, suggesting that the RNase L system is the primary sensor pathway for endogenous dsRNA that leads to cell death.</p> |
DOI | 10.7554/eLife.25687 |
Alternate Journal | Elife |
PubMed ID | 28362255 |
PubMed Central ID | PMC5404912 |
Grant List | T32 AI007324 / AI / NIAID NIH HHS / United States R01 GM110161 / GM / NIGMS NIH HHS / United States K00 CA212468 / CA / NCI NIH HHS / United States R01 AI104887 / AI / NIAID NIH HHS / United States R01 NS081008 / NS / NINDS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States R01 CA044059 / CA / NCI NIH HHS / United States F99 CA212468 / CA / NCI NIH HHS / United States |