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

IF 16.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nucleic Acids Research Pub Date : 2025-04-08 DOI:10.1093/nar/gkaf261

Juan José Berlanga, Tania Matamoros, Miguel Rodríguez Pulido, Margarita Sáiz, Mercedes Núñez Bayón, René Toribio, Iván Ventoso

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引用次数: 0

Abstract

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 sensitivity to NSP1. Translation of SARS-CoV-2 mRNAs escapes NSP1-mediated inhibition by a proper combination of suboptimal codon usage and slotting-prone 5′ UTR. Thus, the prevalence of nonoptimal codons found in SARS-CoV-2 and other coronavirus genomes is favored by the distinctive effect that NSP1 plays on translation and mRNA stability.

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来源期刊

Nucleic Acids Research 生物-生化与分子生物学

CiteScore

27.10

自引率

4.70%

发文量

1057

审稿时长

2 months

期刊介绍： Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.