假尿苷化的功能及治疗应用。
Functions and therapeutic applications of pseudouridylation.
作者信息
Luo Nan, Huang Qiang, Zhang Meiling, Yi Chengqi
机构信息
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
College of Biological Sciences, China Agricultural University, Beijing, China.
出版信息
Nat Rev Mol Cell Biol. 2025 May 20. doi: 10.1038/s41580-025-00852-1.
The success of using pseudouridine (Ψ) and its methylation derivative in mRNA vaccines against SARS-CoV-2 has sparked a renewed interest in this RNA modification, known as the 'fifth nucleotide' of RNA. In this Review, we discuss the emerging functions of pseudouridylation in gene regulation, focusing on how pseudouridine in mRNA, tRNA and ribosomal RNA (rRNA) regulates translation. We also discuss the effects of pseudouridylation on RNA secondary structure, pre-mRNA splicing, and in vitro mRNA stability. In addition to nuclear-genome-encoded RNAs, pseudouridine is also present in mitochondria-encoded rRNA, mRNA and tRNA, where it has different distributions and functions compared with their nuclear counterparts. We then discuss the therapeutic potential of programmable pseudouridylation and mRNA vaccine optimization through pseudouridylation. Lastly, we briefly describe the latest quantitative pseudouridine detection methods. We posit that pseudouridine is a highly promising modification that merits further epitranscriptomics investigation and therapeutic application.
在针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的信使核糖核酸（mRNA）疫苗中使用假尿苷（Ψ）及其甲基化衍生物取得的成功，引发了人们对这种被称为RNA“第五种核苷酸”的RNA修饰的新兴趣。在这篇综述中，我们讨论了假尿苷化在基因调控中的新兴功能，重点关注信使核糖核酸、转运核糖核酸（tRNA）和核糖体核糖核酸（rRNA）中的假尿苷如何调节翻译。我们还讨论了假尿苷化对RNA二级结构、前体信使核糖核酸剪接以及体外信使核糖核酸稳定性的影响。除了核基因组编码的RNA外，假尿苷也存在于线粒体编码的rRNA、mRNA和tRNA中，与它们在细胞核中的对应物相比，其分布和功能有所不同。然后，我们讨论了可编程假尿苷化的治疗潜力以及通过假尿苷化优化mRNA疫苗。最后，我们简要介绍了最新的假尿苷定量检测方法。我们认为，假尿苷是一种非常有前景的修饰，值得进一步开展表观转录组学研究和治疗应用。
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