Figure 3.

The RBP partners of cGAS. (A) The binding of TRIM56 to cGAS induces the Lys335 monoubiquitylation of cGAS, thereby increasing the dimerization and DNA-binding activity of cGAS. (B) ZCCHC3 acts as a co-sensor for the recognition of dsDNA by cGAS. Briefly, ZCCHC3 binds to dsDNA and interacts with cGAS in the cytoplasm, enhancing the binding of cGAS to dsDNA and the formation of a large cGAS complex. (C) PCBP1 is a critical regulator of DNA recognition by cGAS. PCBP1 was recruited to cGAS in a viral infection-dependent manner. PCBP1 bound to DNA and enhanced cGAS binding to dsDNA. (D) G3BP1 physically interacts with and primes cGAS for efficient activation. G3BP1 enhanced the DNA binding of cGAS by promoting the formation of large cGAS complexes. (E) The binding of cytosolic dsDNA to cGAS induces a robust phase transition to liquid-like droplets, which are considered as microreactors with concentrated RNA and RBPs, suggesting a potential link between cGAS and RBPs. (F) NONO is an essential sensor of the HIV capsid in the nucleus. NONO forms a complex with cGAS in the nucleus. Detection of the nuclear viral capsid by NONO promotes the recognition of DNA by cGAS.