SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression.

SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression.

Publication date: Sep 21, 2023

Viruses use microRNAs (miRNAs) to impair the host antiviral response and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. miRNAs inhibit translation initiation of their target mRNAs by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5′-cap structure. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for blocking translation of the Ifn1-b mRNA that encodes the cytokine Interferon-cDF, and thereby impairs the host antiviral response. However, it is not known whether NSP2 also affects miRNA-mediated silencing. Here, we demonstrate the pervasive augmentation of the miRNA-mediated translational repression of cellular mRNAs by NSP2. We show that NSP2 interacts with Argonaute 2, the core component of the miRNA-Induced Silencing Complex (miRISC) via GIGYF2 and enhances the translational repression mediated by natural miRNA binding sites in the 3′ UTR of cellular mRNAs. Our data reveal an additional layer of the complex mechanism by which SARS-CoV-2 and likely other coronaviruses manipulate the host gene expression program through co-opting the host miRNA-mediated silencing machinery.

Concepts Keywords
Antiviral 4EHP
Argonaute GIGYF2
Coronaviruses MicroRNA
Microrna MRNA translation
Translational NSP2


Type Source Name
disease VO SARS-CoV-2 protein
disease MESH repression
disease IDO host
disease MESH viral infection
disease VO Severe acute respiratory syndrome coronavirus 2
pathway REACTOME Translation

Original Article

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