HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

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.
Complete list of metadata

https://hal-cnrs.archives-ouvertes.fr/hal-03100138
Contributor : Jean-Michel Camadro Connect in order to contact the contributor
Submitted on : Wednesday, January 6, 2021 - 4:50:21 PM
Last modification on : Monday, May 9, 2022 - 1:52:19 PM

File

2019_Sanchez-David-RY_Sci.Sign...
Publisher files allowed on an open archive

Identifiers

Citation

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 (AAAS), 2019, 12 (601), pp.eaar3993. ⟨10.1126/scisignal.aar3993⟩. ⟨hal-03100138⟩

Share

Metrics

Record views

53

Files downloads

264