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. 2018 Jun 20;9:1398. doi: 10.3389/fimmu.2018.01398

Figure 7.

Figure 7

Model of avian and mammalian OASL involvement in RNase L and RIG-I signaling. As a sensor, ancient and enzymatic OASL in birds and mammals contain three aspartic acids (D), which are homologous to D75-D77-D148 in hOAS1 and required to synthesize 2–5As, and three key positively charged amino acids (R/K-K/R-K), which are homologous to R195-K199-K205 in human 2′–5′-oligoadenylate synthetase 1 (OAS1). Both avian and mammalian OASLs develop the potential ability to switch the OAS/RNase L and OASL/RIG-I signaling. In natural, avian OASL activates and magnifies the OAS/RNase L pathway to exert antiviral activity in an UBL-dependent manner, where both its OAS-like domain (OLD) and UBL domains bind dsRNA. While some enzymatic mammalian OASLs activate and magnify the OAS/RNase L pathway to exert antiviral activity in an UBL-independent manner, where only their OLD domains bind dsRNA and synthesizes 2–5A like human OAS1. Some non-enzymatic mammalian OASLs lose 2–5A activity, switch to activate, and enhance RIG-I signaling to inhibit the replications of RNA viruses in a UBL-dependent manner when their three conserved D sites are mutated. Such natural switching between the OAS/RNase L and OASL/RIG-I using OASL molecules were recently, thus, both avian and mammalian OASL may reversibly to activate and magnify one of the above signaling when we introduce mutations at three conserved D sites. Five-pointed star (red): D residue; Five-pointed star (blue): D sites serving as metal ion ligands were mutated to A residue, or E81, E83, and T152 site in hOASL; Four-pointed star (black): three key positively charged amino acids; Four-pointed star (green): three key positively charged amino acids (RKK or KKK) were mutated to E. Abbreviations: OLD, OAS-like domain; UBL, ubiquitin-like domain; ARD, ankyrin repeat domain; KEN, kinase-extension-nuclease domain; CARD, caspase activation and recruitment domain; CTD, carboxy-terminal domain; ISRE, interferon-stimulated response element; MAVS, mitochondrial antiviral signaling protein; IRF, IFN-regulatory factor; ssRNA, single-stranded RNA; dsRNA, double-stranded RNA.