The human E3 ligase RNF185 is a regulator of the SARS-CoV-2 envelope protein

Charles Zou; Hojong Yoon; Paul M C Park; J J Patten; Jesse Pellman; Jeannie Carreiro; Jonathan M Tsai; Yen-Der Li; Shourya S Roy Burman; Katherine A Donovan; Jessica Gasser; Adam S Sperling; Radosław P Nowak; Eric S Fischer; Robert A Davey; Benjamin L Ebert; Mikołaj Słabicki

doi:10.1016/j.isci.2023.106601

The human E3 ligase RNF185 is a regulator of the SARS-CoV-2 envelope protein

iScience. 2023 May 19;26(5):106601. doi: 10.1016/j.isci.2023.106601. Epub 2023 Apr 8.

Authors

Charles Zou¹, Hojong Yoon^{1

2}, Paul M C Park^{1

2}, J J Patten³, Jesse Pellman^{1

2}, Jeannie Carreiro^{1

2}, Jonathan M Tsai^{1

2}, Yen-Der Li^{1

2}, Shourya S Roy Burman^{4

5}, Katherine A Donovan^{4

5}, Jessica Gasser^{1

2}, Adam S Sperling^{1

2

6}, Radosław P Nowak^{4

5}, Eric S Fischer^{4

5}, Robert A Davey³, Benjamin L Ebert^{1

2

7}, Mikołaj Słabicki^{1

2}

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
² Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³ Department of Microbiology, Boston University School of Medicine and NEIDL, Boston University, Boston, MA 02118, USA.
⁴ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
⁵ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
⁶ Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Howard Hughes Medical Institute, Boston, MA, USA.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks multiple human proteins during infection and viral replication. To examine whether any viral proteins employ human E3 ubiquitin ligases, we evaluated the stability of SARS-CoV-2 proteins with inhibition of the ubiquitin proteasome pathway. Using genetic screens to dissect the molecular machinery involved in the degradation of candidate viral proteins, we identified human E3 ligase RNF185 as a regulator of protein stability for the SARS-CoV-2 envelope protein. We found that RNF185 and the SARS-CoV-2 envelope co-localize to the endoplasmic reticulum (ER). Finally, we demonstrate that the depletion of RNF185 significantly increases SARS-CoV-2 viral titer in a cellular model. Modulation of this interaction could provide opportunities for novel antiviral therapies.

Keywords: Cell biology; Virology.

Grants and funding

K08 CA252174/CA/NCI NIH HHS/United States