Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5

Brisse, Morgan; Ly, Hinh

that proteins with similar functions may have evolved separately in other species from ancient helicase-DExD/H proteins, implicating RNA-mediated defense responses as a potentially universal biological function. A RIG-I homolog has recently been found in a planarian that is able to activate downstream inflammatory genes in the absence of the traditional CARD domains (350) , and a similar homolog in Caenorhabditis elegans has been proposed to mediate anti-viral RNAi by complexing with Dicer and catalyzing their translocation on the viral genome (351) . Additionally, insects have been found to primarily respond to RNA viruses by RNAi mediated by Dicer proteins (352) . Dicer may potentially mediate dsRNA-activated anti-viral signaling pathways that is independent of RNAi pathways, as has been found to be the case for the expanded CAG-repeat dsRNA (353) . Pattern recognition receptors (PRRs) that respond to viral RNA have not yet been found outside of the animal kingdom, as RLRlike proteins in prokaryotes do not have CARD domains and the PRRs in plants found so far are surface-receptor kinases that respond to external molecular elements of bacteria (354) [similar to the mammalian toll-like receptors (TLRs)]. However, RNA silencing has been demonstrated to be an important anti-viral strategy in plants (354, 355) and certain Arabidopsis mutants appear to be more susceptible to infection by RNA viruses (356) .