tetano
Editor, Senior Moderator
mBio
. 2022 Feb 1;e0316821.
doi: 10.1128/mbio.03168-21. Online ahead of print.
The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release
Zhen Yuan[SUP] #[/SUP][SUP] 1 [/SUP], Bing Hu[SUP] #[/SUP][SUP] 2 [/SUP], Hurong Xiao[SUP] 1 [/SUP], Xuan Tan[SUP] 1 [/SUP], Yan Li[SUP] 3 [/SUP], Ke Tang[SUP] 1 [/SUP], Yonghui Zhang[SUP] 4 [/SUP], Kun Cai[SUP] 2 [/SUP], Binbin Ding[SUP] 1 5 [/SUP]
Affiliations
Abstract
As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a membrane protein (M) that mediates viral release from cellular membranes. However, the molecular mechanisms of SARS-CoV-2 virion release remain poorly understood. In the present study, we performed RNA interference (RNAi) screening and identified the E3 ligase RNF5, which mediates the ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of the viral envelope protein (E) with M, whereas the deubiquitinating enzyme POH1 negatively regulates this process. The M-E complex ensures the uniform size of viral particles for viral maturation and mediates virion release. Moreover, M traffics from the Golgi apparatus to autophagosomes and uses autophagosomes for virion release, and this process is dependent on RNF5-mediated ubiquitin modification and M-E interaction. These results demonstrate that ubiquitin modification of SARS-CoV-2 M stabilizes the M-E complex and uses autophagosomes for virion release. IMPORTANCE 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.
Keywords: RNF5; SARS-CoV-2; autophagy; release; ubiquitination; virus-like particles.
. 2022 Feb 1;e0316821.
doi: 10.1128/mbio.03168-21. Online ahead of print.
The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release
Zhen Yuan[SUP] #[/SUP][SUP] 1 [/SUP], Bing Hu[SUP] #[/SUP][SUP] 2 [/SUP], Hurong Xiao[SUP] 1 [/SUP], Xuan Tan[SUP] 1 [/SUP], Yan Li[SUP] 3 [/SUP], Ke Tang[SUP] 1 [/SUP], Yonghui Zhang[SUP] 4 [/SUP], Kun Cai[SUP] 2 [/SUP], Binbin Ding[SUP] 1 5 [/SUP]
Affiliations
- PMID: 35100873
- DOI: 10.1128/mbio.03168-21
Abstract
As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a membrane protein (M) that mediates viral release from cellular membranes. However, the molecular mechanisms of SARS-CoV-2 virion release remain poorly understood. In the present study, we performed RNA interference (RNAi) screening and identified the E3 ligase RNF5, which mediates the ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of the viral envelope protein (E) with M, whereas the deubiquitinating enzyme POH1 negatively regulates this process. The M-E complex ensures the uniform size of viral particles for viral maturation and mediates virion release. Moreover, M traffics from the Golgi apparatus to autophagosomes and uses autophagosomes for virion release, and this process is dependent on RNF5-mediated ubiquitin modification and M-E interaction. These results demonstrate that ubiquitin modification of SARS-CoV-2 M stabilizes the M-E complex and uses autophagosomes for virion release. IMPORTANCE 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.
Keywords: RNF5; SARS-CoV-2; autophagy; release; ubiquitination; virus-like particles.