LGP2 binds to PACT to regulate RIG-I– and MDA5-mediated antiviral responses - Archive ouverte HAL Access content directly
Journal Articles Science Signaling Year : 2019

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

(1) , (1) , (1) , (2) , (1) , , (3) , (3) , (4) , , (1) , (1) , (1)
1
2
3
4

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.
Fichier principal
Vignette du fichier
2019_Sanchez-David-RY_Sci.Signal_2019_31575732_w-Spplt_(LGP2 binds to PACT to regulate RIG-I- and MDA5-mediated antiviral responses).pdf (10.24 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

hal-03100138 , version 1 (06-01-2021)

Identifiers

Cite

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, 2019, 12 (601), pp.eaar3993. ⟨10.1126/scisignal.aar3993⟩. ⟨hal-03100138⟩
56 View
357 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More