Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex

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)...

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Autores principales: Kato, Koki, Ikliptikawati, Dini Kurnia, Kobayashi, Akiko, Kondo, Hiroya, Lim, Keesiang, Hazawa, Masaharu, Wong, Richard W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733692/
https://www.ncbi.nlm.nih.gov/pubmed/33360543
http://dx.doi.org/10.1016/j.bbrc.2020.11.115
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author Kato, Koki
Ikliptikawati, Dini Kurnia
Kobayashi, Akiko
Kondo, Hiroya
Lim, Keesiang
Hazawa, Masaharu
Wong, Richard W.
author_facet Kato, Koki
Ikliptikawati, Dini Kurnia
Kobayashi, Akiko
Kondo, Hiroya
Lim, Keesiang
Hazawa, Masaharu
Wong, Richard W.
author_sort Kato, Koki
collection PubMed
description 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.
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spelling pubmed-77336922020-12-14 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. Biochem Biophys Res Commun Article 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. Elsevier Inc. 2021-01-15 2020-12-13 /pmc/articles/PMC7733692/ /pubmed/33360543 http://dx.doi.org/10.1016/j.bbrc.2020.11.115 Text en © 2020 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Kato, Koki
Ikliptikawati, Dini Kurnia
Kobayashi, Akiko
Kondo, Hiroya
Lim, Keesiang
Hazawa, Masaharu
Wong, Richard W.
Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex
title Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex
title_full Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex
title_fullStr Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex
title_full_unstemmed Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex
title_short Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex
title_sort overexpression of sars-cov-2 protein orf6 dislocates rae1 and nup98 from the nuclear pore complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733692/
https://www.ncbi.nlm.nih.gov/pubmed/33360543
http://dx.doi.org/10.1016/j.bbrc.2020.11.115
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