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Gadd45β is critical for regulation of type I interferon signaling by facilitating G3BP-mediated stress granule formation

ABSTRACT: Stress granules (SGs) constitute a signaling hub that plays a critical role in type I interferon responses. Here, we report that growth arrest and DNA damage-inducible beta (Gadd45β) act as a novel positive regulator of SGs-mediated interferon signaling by targeting G3BP upon RNA virus infection. Gadd45β deficiency markedly impairs SG formation and SG-mediated activation of interferon signaling in vitro. Gadd45β knockout mice are highly susceptible to RNA virus infection and their ability to produce interferon and cytokines is severely impaired. Specifically, Gadd45β interacts with the RNA-binding domain of G3BP, leading to conformational expansion of G3BP1 via dissolution of its autoinhibitory electrostatic intramolecular interaction. The acidic loop 1- and RNA-binding properties of Gadd45β markedly increase the conformational expansion and RNA-binding affinity of the G3BP1-Gadd45β complex, thereby promoting assembly of SGs. These findings suggest a role for Gadd45β as a new component and critical regulator of G3BP1-mediated SG formation which facilitates RLR-mediated interferon signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE242462 | GEO | 2024/09/06

REPOSITORIES: GEO

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