Zhang et al. recently reported that upon RNA virus infection, the JMJD6 recruits RNF5 from cytoplasm to the nucleus for degrading activated IRF3 via K48-linked poly-ubiquitination, maintaining the immune system homeostasis.273 Qin et al. indicated that during the late phase of viral infection, RNF26 negatively modulates the virus-triggered IFN-I production by indirectly impairing the IRF3 stability in an autophagy-dependent degradation manner.262 However, the relevant mechanism by which RNF26 mediates the autophagic degradation of IRF3 remains less known. The gene discussed is IRF3; the disease is viral infectious disease.