Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland; Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg-University Mainz, Staudingerweg 5, 55128 Mainz, Germany.
Curr Opin Genet Dev. 2024 Aug;87:102210. doi: 10.1016/j.gde.2024.102210. Epub 2024 Jun 3.
Pseudouridine (Ψ), the most abundant RNA modification, plays a role in pre-mRNA splicing, RNA stability, protein translation efficiency, and cellular responses to environmental stress. Dysregulation of pseudouridylation is linked to human diseases. This review explores recent insights into the role of RNA pseudouridylation alterations in human disorders and the therapeutic potential of Ψ. We discuss the impact of the reduction of Ψ levels in ribosomal, messenger, and transfer RNA in RNA processing, protein translation, and consequently its role in neurodevelopmental diseases and cancer. Furthermore, we review the success of N1-methyl-Ψ messenger RNA vaccines against COVID-19 and the development of RNA-guided pseudouridylation enzymes for treating genetic diseases caused by premature stop codons.
假尿嘧啶核苷（Ψ）是最丰富的 RNA 修饰物，在 mRNA 剪接、RNA 稳定性、蛋白质翻译效率以及细胞对环境应激的反应中发挥作用。假尿嘧啶核苷的失调与人类疾病有关。本综述探讨了 RNA 假尿嘧啶核苷改变在人类疾病中的作用以及 Ψ 的治疗潜力。我们讨论了降低核糖体、信使 RNA 和转运 RNA 中 Ψ 水平对 RNA 加工、蛋白质翻译的影响，以及其在神经发育性疾病和癌症中的作用。此外，我们还回顾了 N1-甲基-Ψ 信使 RNA 疫苗在对抗 COVID-19 中的成功应用，以及 RNA 指导的假尿嘧啶核苷合成酶在治疗由提前终止密码子引起的遗传疾病方面的发展。
