Cell https://doi.org/10.1016/j.cell.2019.03.017 (2019)

The E3 ligase RIPLET is required for activation of the viral dsRNA receptor RIG-I. In Cell, Hur and colleagues show that RIPLET uses its dimeric structure to recognize and ubiquitinate pre-oligomerized RIG-I bound to dsRNA and promotes antiviral signaling in a manner dependent on the length of the RNA. RIPLET binds and conjugates K63 ubiquitin on RIG-I–dsRNA complexes but not on free RIG-I. RIPLET needs to be a dimer to bind RIG-I, requires dsRNAs long enough to accommodate two RIG-I molecules (at least 21 bp) and induces maximum ubiquitination of RIG-I on 30- to 40-bp dsRNAs. On long dsRNA (160 or 512 bp), RIPLET bridges multiple RIG-I filaments through inter-filament binding and induces filamentation of the adaptor MAVS independently of the ubiquitination of RIG-I. The filament-bridging activity and ubiquitination activity of RIPLET are synergistic in amplifying RIG-I signaling.