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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/7627| The SARS-CoV-2 protein NSP2 impairs the microRNA-induced silencing capacity of human cells | |
| Limei Zou Clara Moch Marc Graille Clément Chapat | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2022.01.25.477753 | |
| https://www.biorxiv.org/content/10.1101/2022.01.25.477753v1 | |
| The coronavirus SARS-CoV-2 is the cause of the ongoing pandemic of COVID-19. Given the absence of effective treatments against SARS-CoV-2, there is an urgent need for a molecular understanding of how the virus influences the machineries of the host cell. The SARS-CoV-2 generates 16 Non-Structural Proteins (NSPs) through proteolytic cleavage of a large precursor protein. In the present study, we focused our attention on the SARS-CoV-2 protein NSP2, whose role in the viral pathogenicity is poorly understood. Recent proteomic studies shed light on the capacity of NSP2 to bind the 4EHP-GIGYF2 complex, a key factor involved in microRNA-mediated silencing of gene expression in human cells. In order to gain a better understanding of the function of NSP2, we attempted to identify the molecular basis of its interaction with 4EHP-GIGYF2. Our data demonstrate that NSP2 physically associates with the endogenous 4EHP-GIGYF2 complex in the cytoplasm. Using co-immunoprecipitation and in vitro interaction assays, we identified both 4EHP and a central segment in GIGYF2 as binding sites for NSP2. We also provide functional evidence that NSP2 impairs the function of GIGYF2 in mediating mRNA silencing using reporter-based assays, thus leading to a reduced activity of microRNAs. Altogether, these data reveal the profound 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. | |
| medRxiv and bioRxiv | |
| 26-01-2022 | |
| Preimpreso | |
| www.biorxiv.org | |
| Inglés | |
| Epidemia COVID-19 | |
| Público en general | |
| VIRUS RESPIRATORIOS | |
| Versión publicada | |
| publishedVersion - Versión publicada | |
| Aparece en las colecciones: | Artículos científicos |
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| The SARS COV2 protein NSP2 impairs the microRNA induced silencing capacity of human.pdf | 3.23 MB | Adobe PDF | Visualizar/Abrir |