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

Brisse, Morgan; Ly, Hinh

A recent study showed that Riplet rather than TRIM25 was primarily responsible for ubiquitinating and activating RIG-I (103). However, there are several factors to take into consideration with this study. These recent results were obtained using KO 293T and mouse embryonic fibroblast (MEF) cells and that it was not clear whether K63 ubiquitination occurred at other known lysine sites in RIG-I. The question remains whether Riplet can ubiquitinate other lysine residues in the absence of TRIM25. Additionally, in-situ experiments comparing RIG-I ubiquitination by Riplet and TRIM25 utilized an E2 enzyme (103) that had been found to be specific for Riplet (107) . While the E2 that utilizes TRIM25 has not yet been identified, TRIM25 has been shown to ubiquitinate RIG-I in-situ when a general mixture of E2 proteins was used (108) . The protein levels of TRIM25 may also have to be at a certain level in order for it to productively ubiquitinate RIG-I, as the ubiquitin protease USP15 deubiquitinates TRIM25 at later time points in viral infection (109) .