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

Brisse, Morgan; Ly, Hinh

On the other hand, other studies have shown that RIG-I can interact with monophosphate dsRNA to a certain degree, as has been found to be the case for short synthetic dsRNA with a 5 ′ and 3 ′ monophosphate group (69), poly(I:C) digested with RNase III (76) [which generates 5 ′ mono-phosphate/3 ′ -OH dsRNA (178) ] and HCV RNA (179) and mitochondrial RNA [in the p53 deficient mice (180) ] digested with RNase L [which produces 5 ′ OH and 3 ′ mono-phosphate dsRNA at subnanomolar levels (181) , as has been found to be the case for HCV RNA (179) .] It appears that the 5 ′ monophosphate is the determinate feature for RIG-I activation independently of the 5 ′ or 3 ′ OH group in all these cases. A possible explanation for the discrepancy between the studies was that higher order RNA structures might compensate for the less optimal 5 ′ and 3 ′ ends, as monophosphate dsRNA that did not contain stem-loop structures did not activate RIG-I and RNA regions repetitive in certain nucleotides had been found to be critical for RIG-I activation (179) . Future studies are required to further characterize the behavior of RIG-I with these RNA species.