The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release
Zhen Yuan, Bing Hu, Hurong Xiao, Xuan Tan, Yan Li, Ke Tang, Yonghui Zhang, Kun Cai, Binbin Ding
Abstract
Enveloped virus particles are released from the membranes of host cells, and viral membrane proteins (M) are critical for this process. A better understanding of the molecular mechanisms of SARS-CoV-2 assembly and budding is critical for the development of antiviral therapies. Envelope protein (E) and M of SARS-CoV-2 form complexes to mediate viral assembly and budding. RNF5 was identified to play a role as the E3 ligase, and POH1 was demonstrated to function as the deubiquitinating enzyme of SARS-CoV-2 M. The two components collectively regulate the interaction of M with E to promote viral assembly and budding. Ubiquitinated M uses autophagosomes for viral release. Our findings provide insights into the mechanisms of SARS-CoV-2 assembly and budding, demonstrating the importance of ubiquitination modification and autophagy in viral replication.