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LGP2 binds to PACT to regulate RIG-I– and MDA5-mediated antiviral responses

Abstract : The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) RIG-I, MDA5, and LGP2 stimulate inflammatory and antiviral responses by sensing nonself RNA molecules produced during viral replication. Here, we investigated how LGP2 regulates the RIG-I-and MDA5-dependent induction of type I interferon (IFN) signaling and showed that LGP2 interacted with different components of the RNA-silencing machinery. We identified a direct proteinprotein interaction between LGP2 and the IFN-inducible, double-stranded RNA binding protein PACT. The LGP2-PACT interaction was mediated by the regulatory C-terminal domain of LGP2 and was necessary for inhibiting RIG-I-dependent responses and for amplifying MDA5-dependent responses. We described a point mutation within LGP2 that disrupted the LGP2-PACT interaction and led to the loss of LGP2-mediated regulation of RIG-I and MDA5 signaling. These results suggest a model in which the LGP2-PACT interaction regulates the inflammatory responses mediated by RIG-I and MDA5 and enables the cellular RNA-silencing machinery to coordinate with the innate immune response.
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https://hal-cnrs.archives-ouvertes.fr/hal-03100138
Contributor : Jean-Michel Camadro <>
Submitted on : Wednesday, January 6, 2021 - 4:50:21 PM
Last modification on : Saturday, June 19, 2021 - 4:17:38 AM

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Raul Sanchez David, Chantal Combredet, Valérie Najburg, Gaël Millot, Guillaume Beauclair, et al.. LGP2 binds to PACT to regulate RIG-I– and MDA5-mediated antiviral responses. Science Signaling, American Association for the Advancement of Science, 2019, 12 (601), pp.eaar3993. ⟨10.1126/scisignal.aar3993⟩. ⟨hal-03100138⟩

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