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PKR-dependent cytosolic cGAS foci are necessary for intracellular DNA sensing
- Source :
- Science Signaling. 12
- Publication Year :
- 2019
- Publisher :
- American Association for the Advancement of Science (AAAS), 2019.
-
Abstract
- Cyclic GMP-AMP synthase (cGAS) is a major sensor of cytosolic DNA from invading pathogens and damaged cellular organelles. Activation of cGAS promotes liquid-like phase separation and formation of membraneless cytoplasmic structures. Here, we found that cGAS bound G3BP1, a double-stranded nucleic acid helicase involved in the formation of stress granules. Loss of G3BP1 blocked subcellular cGAS condensation and suppressed the interferon response to intracellular DNA and DNA virus particles in cells. Furthermore, an RNA-dependent association with PKR promoted G3BP1 foci formation and cGAS-dependent interferon responses. Together, these results indicate that PKR promotes the formation of G3BP1-dependent, membraneless cytoplasmic structures necessary for the DNA-sensing function of cGAS in human cells. These data suggest that there is a previously unappreciated link between nucleic acid sensing pathways, which requires the formation of specialized subcellular structures.
- Subjects :
- THP-1 Cells
Biochemistry
eIF-2 Kinase
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Stress granule
Humans
Poly-ADP-Ribose Binding Proteins
Molecular Biology
030304 developmental biology
0303 health sciences
biology
Chemistry
DNA Helicases
Helicase
DNA virus
DNA
Cell Biology
Nucleotidyltransferases
Cell biology
Cytosol
RNA Recognition Motif Proteins
030220 oncology & carcinogenesis
Nucleic acid
biology.protein
Signal transduction
RNA Helicases
Intracellular
Signal Transduction
Subjects
Details
- ISSN :
- 19379145 and 19450877
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Science Signaling
- Accession number :
- edsair.doi.dedup.....e7eb08e24fa4cd72976d2628c16c95ec