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The cGAS-STING pathway plays a central role in the detection of DNA in the cytosol of mammalian cells and activation of immunity. Although the early evolutionary origin of this pathway in animals has been noted, its ancestral functions have remained elusive so far. We review here new findings in invertebrates establishing a role in sensing and signaling infection, triggering potent transcriptional responses, in addition to autophagy. Results from flies and moths/butterflies point to the importance of STING signaling in antiviral immunity in insects. The recent characterization of cGAS-like receptors in Drosophila reveals the plasticity of this family of pattern-recognition receptors, able to accommodate ligands different from DNA and to produce cyclic dinucleotides beyond 2'3'-cGAMP., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Induction of antiviral immunity in vertebrates and invertebrates relies on members of the RIG-I-like receptor and Dicer families, respectively. Although these proteins have different size and domain composition, members of both families share a conserved DECH-box helicase domain. This helicase, also known as a duplex RNA activated ATPase, or DRA domain, plays an important role in viral RNA sensing. Crystallographic and electron microscopy studies of the RIG-I and Dicer DRA domains indicate a common structure and that similar conformational changes are induced by dsRNA binding. Genetic and biochemical studies on the function and regulation of DRAs reveal similarities, but also some differences, between viral RNA sensing mechanisms in nematodes, flies and mammals., (Copyright © 2015 Elsevier Ltd. All rights reserved.)