IRF3 signaling depends on a translocation of signaling upon proteasomal-degradation of MAVS. In non-activated cells, MAVS is associated to mitochondria through its C-terminal transmembrane domain. RLR activation induces MAVS oligomerization and aggregation  (to simplify the model, only two MAVS molecules are shown as forming an aggregate), then MAVS recruits TRAF3 and other E3 ubiquitin ligases which function to catalyze Lys 63-linked polyubiquitination of target proteins including TRAF3 itself. The Lys 63-linked polyubiquitin chains (in green) recruit NEMO which in turn binds to TBK1 and TBK1 is activated. Concomitantly, TRIM25 induces Lys 48-linked polyubiquitination (in red) of MAVS. The proteasomal degradation of MAVS results in the translocation of the MAVS-assembled complex into the cytosol where activated TBK1 phosphorylates IRF3 to promote type I IFN production.