RNASeq of human bronchial epithelial (HBE) cells with cGAS-siRNA transfected
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE185523 | GEO | 2022/10/01
REPOSITORIES: GEO
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Project description:RNASeq of human bronchial epithelial (HBE) cells with cGAS-siRNA transfected
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Project description:The cGAS-STING pathway, a central component of the innate immune system, senses cytosolic DNA and induces interferon-stimulated genes (ISGs) to mediate inflammation. Here we report the unexpected discovery that cGAS senses dysfunctional translation. Purified ribosomes interact with and stimulate recombinant cGAS catalytic activity in vitro. Disruption of the ribosome-associated protein quality control pathway, which detects and resolves ribosome collisions, results in cGAS- and STING-dependent ISG expression, and cause the re-localization of cGAS from the nucleus to the cytosol. Other orthogonal perturbations that lead to elevated levels of collided ribosomes cause re-localization of cGAS as well. Thus, the cGAS-STING pathway senses and responds to translation stress. These findings have implications for the inflammatory responses to viral infection and tumorigenesis, both of which substantially reprogram cellular protein synthesis.
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