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The differential effect of SARS-CoV-2 NSP1 on mRNA translation and stability reveals new insights linking ribosome recruitment, codon usage, and virus evolution

Nucleic Acids Research. 2025-04; 
Juan José Berlanga, Tania Matamoros, Miguel Rodríguez Pulido, Margarita Sáiz, Mercedes Núñez Bayón, René Toribio, Iván Ventoso Universidad Autónoma de Madrid
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PCR Cloning and Subcloning All variants of pG-less-RL, p5′ L-N, p5′L-RL, p5′L(Gs)-RL, pTISU-EGFP, pSlot-RL, and the recoded versions of pEGFP (pEGFP-1, EGFP-2), pRL (pRL-1, pRL-2 and pRL-3) and N (p5′L-N1, pN1) were obtained from GenScript. Get A Quote

摘要

The nonstructural protein 1 (NSP1) of SARS-CoV-2 blocks the messenger RNA (mRNA) entry channel of the 40S ribosomal subunit, causing inhibition of translation initiation and subsequent degradation of host mRNAs. However, target mRNA specificity and how viral mRNAs escape NSP1-mediated degradation have not been clarified to date. Here we found that NSP1 acts as a translational switch capable of blocking or enhancing translation depending on how preinitiation complex, 43S-PIC, is recruited to the mRNA, whereas NSP1-mediated mRNA degradation mostly depends on codon usage bias. Thus, fast-translating mRNAs with optimal codon usage for human cells that preferentially recruit 43S-PIC by threading showed a dramatic se... More

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