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Article ; Online: Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex.

Kato, Koki / Ikliptikawati, Dini Kurnia / Kobayashi, Akiko / Kondo, Hiroya / Lim, Keesiang / Hazawa, Masaharu / Wong, Richard W

Biochemical and biophysical research communications

2020  Volume 536, Page(s) 59–66

Abstract: ... nuclear rim staining of nucleoporins RAE1 and NUP98. Consequently, this disruption caused aberrant ... Several studies have revealed interactions between SARS-CoV-2 viral proteins and host nucleoporins ... yet their functions are largely unknown. Here, we demonstrate that the open-reading frame 6 (ORF6) of SARS-CoV-2 ...

Abstract The novel human betacoronavirus SARS-CoV-2 has caused an unprecedented pandemic in the 21st century. Several studies have revealed interactions between SARS-CoV-2 viral proteins and host nucleoporins, yet their functions are largely unknown. Here, we demonstrate that the open-reading frame 6 (ORF6) of SARS-CoV-2 can directly manipulate localization and functions of nucleoporins. We found that ORF6 protein disrupted nuclear rim staining of nucleoporins RAE1 and NUP98. Consequently, this disruption caused aberrant nucleocytoplasmic trafficking and led to nuclear accumulation of mRNA transporters such as hnRNPA1. Ultimately, host cell nucleus size was reduced and cell growth was halted.
MeSH term(s) Active Transport, Cell Nucleus ; Cell Nucleus/virology ; Cell Nucleus Size ; HEK293 Cells ; Heterogeneous Nuclear Ribonucleoprotein A1/metabolism ; Humans ; Nuclear Matrix-Associated Proteins/metabolism ; Nuclear Pore Complex Proteins/metabolism ; Nucleocytoplasmic Transport Proteins/metabolism ; SARS-CoV-2 ; Viral Proteins/metabolism
Chemical Substances Heterogeneous Nuclear Ribonucleoprotein A1 ; Nuclear Matrix-Associated Proteins ; Nuclear Pore Complex Proteins ; Nucleocytoplasmic Transport Proteins ; ORF6 protein, SARS-CoV-2 ; RAE1 protein, human ; Viral Proteins ; hnRNPA1 protein, human ; nuclear pore complex protein 98
Language English
Publishing date 2020-12-13
Publishing country United States
Document type Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID 205723-2
ISSN 1090-2104 ; 0006-291X ; 0006-291X
ISSN (online) 1090-2104 ; 0006-291X
ISSN 0006-291X
DOI 10.1016/j.bbrc.2020.11.115
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