The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex

Summary: There is an urgent need for a molecular understanding of how SARS-CoV-2 influences the machineries of the host cell. Herein, we focused our attention on the capacity of the SARS-CoV-2 protein NSP2 to bind the human 4EHP-GIGYF2 complex, a key factor involved in microRNA-mediated silencing of...

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Main Authors: Limei Zou, Clara Moch, Marc Graille, Clément Chapat
Format: Article
Language:English
Published: Elsevier 2022-07-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S258900422200918X
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author Limei Zou
Clara Moch
Marc Graille
Clément Chapat
author_facet Limei Zou
Clara Moch
Marc Graille
Clément Chapat
author_sort Limei Zou
collection DOAJ
description Summary: There is an urgent need for a molecular understanding of how SARS-CoV-2 influences the machineries of the host cell. Herein, we focused our attention on the capacity of the SARS-CoV-2 protein NSP2 to bind the human 4EHP-GIGYF2 complex, a key factor involved in microRNA-mediated silencing of gene expression. Using in vitro interaction assays, our data demonstrate that NSP2 physically associates with both 4EHP and a central segment in GIGYF2 in the cytoplasm. We also provide functional evidence showing that NSP2 impairs the function of GIGYF2 in mediating translation repression using reporter-based assays. Collectively, these data reveal the potential impact of NSP2 on the post-transcriptional silencing of gene expression in human cells, pointing out 4EHP-GIGYF2 targeting as a possible strategy of SARS-CoV-2 to take over the silencing machinery and to suppress host defenses.
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spelling doaj.art-a250a7f1f9014afb979ba32ad2b790a42022-12-22T00:21:34ZengElsevieriScience2589-00422022-07-01257104646The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complexLimei Zou0Clara Moch1Marc Graille2Clément Chapat3Laboratoire de Biologie Structurale de La Cellule (BIOC), CNRS, Ecole Polytechnique, IP Paris, 91128 Palaiseau, FranceLaboratoire de Biologie Structurale de La Cellule (BIOC), CNRS, Ecole Polytechnique, IP Paris, 91128 Palaiseau, FranceLaboratoire de Biologie Structurale de La Cellule (BIOC), CNRS, Ecole Polytechnique, IP Paris, 91128 Palaiseau, FranceLaboratoire de Biologie Structurale de La Cellule (BIOC), CNRS, Ecole Polytechnique, IP Paris, 91128 Palaiseau, France; Corresponding authorSummary: There is an urgent need for a molecular understanding of how SARS-CoV-2 influences the machineries of the host cell. Herein, we focused our attention on the capacity of the SARS-CoV-2 protein NSP2 to bind the human 4EHP-GIGYF2 complex, a key factor involved in microRNA-mediated silencing of gene expression. Using in vitro interaction assays, our data demonstrate that NSP2 physically associates with both 4EHP and a central segment in GIGYF2 in the cytoplasm. We also provide functional evidence showing that NSP2 impairs the function of GIGYF2 in mediating translation repression using reporter-based assays. Collectively, these data reveal the potential impact of NSP2 on the post-transcriptional silencing of gene expression in human cells, pointing out 4EHP-GIGYF2 targeting as a possible strategy of SARS-CoV-2 to take over the silencing machinery and to suppress host defenses.http://www.sciencedirect.com/science/article/pii/S258900422200918XVirologyMolecular biology
spellingShingle Limei Zou
Clara Moch
Marc Graille
Clément Chapat
The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex
iScience
Virology
Molecular biology
title The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex
title_full The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex
title_fullStr The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex
title_full_unstemmed The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex
title_short The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex
title_sort sars cov 2 protein nsp2 impairs the silencing capacity of the human 4ehp gigyf2 complex
topic Virology
Molecular biology
url http://www.sciencedirect.com/science/article/pii/S258900422200918X
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