病毒RNA阻断环化以逃避宿主密码子使用控制，这一成果由德克萨斯大学刘一课题组经过不懈努力而取得。2025年12月3日，国际知名学术期刊《自然》发表了这一成果。

在这里，该团队表明病毒蛋白在像人类基因一样翻译时受到强密码子图像控制，但是当从病毒复制子翻译时，它们可以逃避这种控制。这种逃避是由多种人类病毒主题中的病毒5'非翻译区（UTRs）介导的，它支持密码子-图像不敏感的翻译。典型的mRNA翻译依赖于密码子映射，需要5' cap, 3' polyA tail及其相关蛋白，这表明mRNA环化在密码子映射对翻译的影响中起作用。

值得注意的是，具有病毒5' UTRs的mRNA的RNA循环恢复了密码子图像依赖的翻译，这主要是由于非最佳密码子图像介导的抑制。这些结果表明，mRNA环状化对于启动密码子图像依赖的翻译至关重要，而病毒RNA通过阻断环状化绕过这一机制，尽管它们的密码子图像较差，但仍能实现有效的翻译。

研究人员表示，密码子位置偏倚是所有基因组的一个基本特征，即某些同义密码子的优先主题。密码子图像在所有生物体中都起着决定基因表达水平的关键作用。几乎所有感染人类的病毒主题都显示出与人类基因不同的密码子图像模式，但它们在宿主细胞中有效地表达它们的蛋白质，以预防疾病和流行病。病毒RNA翻译逃避密码子损伤控制的机制尚不清楚。

附：英文原文

Title: Viral RNA blocks circularization to evade host codon usage control

Author: Liu, Huan, Duan, Jiabin, Garg, Renu, Xie, Pancheng, Liu, Yi

Issue&Volume: 2025-12-03

Abstract: Codon usage bias—the preferential use of certain synonymous codons—is a fundamental feature of all genomes. Codon usage has a key role in determining gene-expression levels in all organisms that have so far been studied1,2,3. Nearly all human-infecting viruses show patterns of codon usage that are distinct from those of human genes—yet they express their proteins efficiently in host cells to cause diseases and pandemics. The mechanism behind this evasion of codon usage control by viral RNA translation is unknown. Here we show that viral proteins are subject to strong codon usage control when they are translated like human genes, but that they can evade this control when translated from viral replicons. This evasion is mediated by viral 5′ untranslated regions (UTRs) in diverse human viruses, which support codon-usage-insensitive translation. Canonical mRNA translation depends on codon usage, requiring the 5′ cap, 3′ polyA tail and their associated proteins, which suggests that mRNA looping has a role in the effect of codon usage on translation. Notably, RNA circularization for mRNAs with viral 5′ UTRs restores codon-usage-dependent translation, owing mainly to non-optimal codon-usage-mediated repression. These results suggest that mRNA circularization is crucial for initiating codon-usage-dependent translation, and that viral RNAs bypass this mechanism by blocking circularization, allowing efficient translation despite their poor codon usage profiles.

DOI: 10.1038/s41586-025-09809-y

Source: https://www.nature.com/articles/s41586-025-09809-y