Toll-like receptors and RIG-I-like receptors recognize different features of RNAs. (A) Toll-like receptors. TLR3 recognizes long double-stranded RNA and signals through the adapter TRIF. TLR7 recognizes single-stranded GU-rich RNA and binds guanosine at a second site. TLR8 recognizes short single-stranded GU-rich RNA and binds uridine at a second site. Both TLR7 and TLR8 signal through the cytosolic adapter MyD88. (B) RIG-I-like receptors sense dsRNA. RIG-I binds double-stranded sequences of at least 10 bp through its helicase domain. The C-terminal domain recognizes the RNA 5′-triphosphate moiety. RNA binding is coupled with derepression of the CARD signaling domains and CARD domain ubiquitination. The CARD domains bind to the adapter protein MAVS. MDA5 binds long double-stranded RNA and assembles into helical filaments along the RNA through its helicase and C-terminal domains. The CARD domains signal through MAVS. (Image was created in BioRender.com.)
