Research ArticleInnate Immunity

PKR-dependent cytosolic cGAS foci are necessary for intracellular DNA sensing

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Science Signaling  26 Nov 2019:
Vol. 12, Issue 609, eaav7934
DOI: 10.1126/scisignal.aav7934

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Aberrant intracellular recognition of self-DNA is controlled by the spatial restriction of the DNA sensor cGAS. To define the interactions that may control cGAS subcellular localization, Hu et al. used mass spectrometry and immunoprecipitation to confirm that endogenous cGAS bound to the nucleotide helicase G3BP1, which is involved in stress granule formation. After DNA stimulation of human cells, cGAS associated in an RNA-dependent manner with G3BP1 and was found in cytoplasmic foci that also contained mRNA and the RNA-dependent kinase PKR. Formation of cytoplasmic cGAS condensates necessary for DNA-stimulated type I interferon production required G3BP1 and PKR activity. Together, these data suggest that G3BP1 cytoplasmic foci act as hubs that may coordinate DNA and RNA nucleic acid sensing.

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