Transcriptomics

Dataset Information

0

Targeting a key disulfide linkage to regulate RIG-I condensation and cytosolic RNA-sensing


ABSTRACT: Maintaining innate immune homeostasis is critical for preventing infections and autoimmune diseases, but the effective interventions are lacking. Here, we identified Cys864-Cys869-mediated intermolecular disulfide-linkage formation as a critical step for human RIG-I activation that can be bidirectionally regulated to control innate immune homeostasis. The viral-stimulated Cys864-Cys869 disulfide-linkage mediates conjugation of an SDS-resistant RIG-I oligomer, which prevents RIG-I degradation by E3 ubiquitin-ligase MIB2 and is necessary for RIG-I to perform liquid-liquid phase separation to compartmentalize downstream signalsome, thereby stimulating IFN-I signaling. The corresponding C865S ‘knock-in’ caused defect of oligomerization and LLPS in mouse RIG-I, which inhibited innate immunity, resulting in increased viral load and mortality in mice. Through generating covalent Cys864-Cys869 linkage by unnatural amino-acid and developing interfering peptide to block Cys864-Cys869 residues, we bidirectionally regulate RIG-I activities in human diseases. These findings provide novel and in-depth insights on mechanism of RIG-I activation, develop methodologies that hold promising implications in clinics

ORGANISM(S): Mus musculus

PROVIDER: GSE283490 | GEO | 2024/12/09

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

| PRJNA1194045 | ENA
2008-11-20 | GSE11650 | GEO
2020-09-09 | GSE157609 | GEO
2020-09-17 | GSE158122 | GEO
2021-01-16 | GSE164882 | GEO
2020-12-01 | GSE162339 | GEO
2024-12-05 | GSE264004 | GEO
2016-08-01 | E-GEOD-51196 | biostudies-arrayexpress
2016-08-01 | GSE51196 | GEO
2019-10-02 | PXD013191 | Pride