摘要：SummaryThere 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. Usingin vitrointeraction 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.Graphical abstractDisplay OmittedHighlights•SARS-CoV-2 NSP2 binds the human 4EHP-GIGYF2 complex•The NSP2/GIGYF2-4EHP interaction involves multiple binding sites•NSP2 reduces the silencing capacity of GIGYF2•NSP2 impairs microRNA-mediated silencingVirology; Molecular biology
