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

iScience (May 2023)

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

Affiliations

Charles Zou: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Hojong Yoon: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Paul M.C. Park: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
J.J. Patten: Department of Microbiology, Boston University School of Medicine and NEIDL, Boston University, Boston, MA 02118, USA
Jesse Pellman: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Jeannie Carreiro: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Jonathan M. Tsai: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Yen-Der Li: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Shourya S. Roy Burman: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Katherine A. Donovan: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Jessica Gasser: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Adam S. Sperling: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Radosław P. Nowak: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Eric S. Fischer: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
Robert A. Davey: Department of Microbiology, Boston University School of Medicine and NEIDL, Boston University, Boston, MA 02118, USA
Benjamin L. Ebert: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA; Corresponding author
Mikołaj Słabicki: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 5
p. 106601

Abstract

Read online

Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords