RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency
In: The EMBO journal, Jg. 41 (2022-01-07), Heft 6
Online
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Zugriff:
RNA 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-Goutieres 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.
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RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency
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Autor/in / Beteiligte Person: | Jorn E Stok ; Oosenbrug, Timo ; Laurens R ter Haar ; Gravekamp, Dennis ; Christian P Bromley ; Zelenay, Santiago ; Caetano Reis e Sousa ; Annemarthe G van der Veen |
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Zeitschrift: | The EMBO journal, Jg. 41 (2022-01-07), Heft 6 |
Veröffentlichung: | 2022 |
Medientyp: | unknown |
ISSN: | 1460-2075 (print) |
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