cGAS-STING: insight on the evolution of a primordial antiviral signaling cassette

Stimulator of interferon genes (STING) functions in the cytosolic DNA-sensing pathway innate immunity mammals. It is activated upon binding cyclic dinucleotide 2?3?-cGAMP, a second messenger produced by enzyme guanosine monophosphate–adenosine monophosphate synthase (cGAS), which acts as receptor for DNA this pathway, and triggers expression interferons other viral stress-induced genes. The ancient origin STING evolution animals had been noted, but its primitive function was speculative. We review here recent advances remarkable history cGAS-STING signaling, establish that cGAS member family cGAS/DncV-like nucleotidyltransferases (CD-NTases). In bacteria, CD-NTases synthesize wide range oligonucleotide messengers response to bacteriophage infections, turn activate variety effector proteins abort phage infection. Among these effectors, some are related STING, revealing an ancestral cassette antiviral host defense. Study signaling invertebrate consistent with early acquisition metazoans CD-NTase- STING-encoding counter universal threat viruses. particular, STING-dependent appears play previously unsuspected important role insects. These discoveries open up interesting perspectives use model organisms decipher emerging aspects biology mammals, such activation interferon-independent responses or regulation nucleus.