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.

环状GMP-AMP合酶（cGAS）是入侵病原体和受损细胞器的胞质DNA的主要传感器。cGAS的激活促进了类似液体的相分离和无膜细胞质结构的形成。在这里，我们发现cGAS结合了G3BP1，G3BP1是参与应激颗粒形成的双链核酸解旋酶。G3BP1的丢失阻止了亚细胞cGAS的凝结，并抑制了干扰素对细胞内DNA和DNA病毒颗粒的应答。此外，与PKR的RNA依赖性缔合促进了G3BP1灶形成和cGAS依赖性干扰素应答。总之，这些结果表明PKR促进了人类细胞中cGAS的DNA感应功能所必需的G3BP1依赖性无膜细胞质结构的形成。