Abstract
In our recent study, we reported the molecular mechanisms of SARS-CoV-2 assembly and budding. Envelope protein (E) and membrane protein (M) of SARS-CoV-2 form complexes that ensure the uniform size of viral particles for viral maturation and budding. The E3 ligase RNF5 mediates the ubiquitination of M at residue K15 and thus enhances M-E interaction, whereas the deubiquitinating enzyme PSMD14/POH1 negatively regulates this process. Intriguingly, we show that M traffics from the Golgi apparatus to an LC3-positive phagophore and exploits the autophagosome to egress, and this process is dependent on RNF5-mediated ubiquitin modification of M and M-E interaction. Our finding suggests that RNF5 and PSMD14 play important roles in SARS-CoV-2 release and SARS-CoV-2-induced exploitation of autophagosomes for egress.