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bioRxiv · 10.1101/2021.02.28.433287

The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release

Yuan, Z.·Ding, B.
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Abstract

As enveloped virus, SARS-CoV-2 membrane protein (M) mediates viral release from cellular membranes, but the molecular mechanisms of SARS-CoV-2 virions release remain poorly understood. Here, we performed RNAi screening and identified the E3 ligase RNF5 which mediates ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of viral envelope (E) with M. M-E complex ensures the uniform size of viral particles for viral maturation and mediates viral release. Moreover, overexpression of M induces complete autophagy which is dependent on RNF5-mediated ubiquitin modification. M inhibits the activity of lysosome protease, and uses autolysosomes for virion release. Consequently, all these results demonstrate that RNF5 mediates ubiquitin modification of SARS-CoV-2 M to stabilize the M-E complex and induce autophagy for virion release.

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Yuan, Z., Ding, B.. 2021-03-01. The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release. https://doi.org/10.1101/2021.02.28.433287

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