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dc.contributor.authorStok, J. E.
dc.contributor.authorOosenbrug, T.
dc.contributor.authorTer Haar, L. R.
dc.contributor.authorGravekamp, D.
dc.contributor.authorBromley, Christian P
dc.contributor.authorZelenay, Santiago
dc.contributor.authorReis, E. S. C.
dc.contributor.authorvan der Veen, A. G.
dc.date.accessioned2022-03-09T13:35:26Z
dc.date.available2022-03-09T13:35:26Z
dc.date.issued2022en
dc.identifier.citationStok JE, Oosenbrug T, Haar LR, Gravekamp D, Bromley CP, Zelenay S, et al. RNA sensing via the RIG‐I‐like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency [Internet]. The EMBO Journal. EMBO; 2022.en
dc.identifier.pmid35156720en
dc.identifier.doi10.15252/embj.2021109760en
dc.identifier.urihttp://hdl.handle.net/10541/625137
dc.description.abstractRNA editing by the adenosine deaminase ADAR1 prevents innate immune responses to endogenous RNAs. In ADAR1-deficient cells, unedited self RNAs form base-paired structures that resemble viral RNAs and inadvertently activate the cytosolic RIG-I-like receptor (RLR) MDA5, leading to an antiviral type I interferon (IFN) response. Mutations in ADAR1 cause Aicardi-Goutières Syndrome (AGS), an autoinflammatory syndrome characterized by chronic type I IFN production. Conversely, ADAR1 loss and the consequent type I IFN production restricts tumor growth and potentiates the activity of some chemotherapeutics. Here, we show that another RIG-I-like receptor, LGP2, also has an essential role in the induction of a type I IFN response in ADAR1-deficient human cells. This requires the canonical function of LGP2 as an RNA sensor and facilitator of MDA5-dependent signaling. Furthermore, we show that the sensitivity of tumor cells to ADAR1 loss requires LGP2 expression. Finally, type I IFN induction in tumor cells depleted of ADAR1 and treated with some chemotherapeutics fully depends on LGP2 expression. These findings highlight a central role for LGP2 in self RNA sensing with important clinical implications.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.15252/embj.2021109760en
dc.titleRNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiencyen
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology, Leiden University Medical Centre, Leiden, The Netherlands. Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK. Immunobiology Laboratory, The Francis Crick Institute, London, UK.en
dc.identifier.journalEmbo Journalen
dc.description.noteen]
refterms.dateFOA2022-06-27T13:49:39Z


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