Zhong Zhenfei, Li Yajie, Sun Qinmiao, Chen Dahua
Institute of Biomedical Research, Yunnan University, Kunming, Yunnan 650500, China.
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Comput Struct Biotechnol J. 2024 Oct 28;23:3771-3779. doi: 10.1016/j.csbj.2024.10.042. eCollection 2024 Dec.
Upstream open reading frames (uORFs) are critical -acting regulators of downstream gene expression. Specifically, uORFs regulate translation by disrupting translation initiation or mediating mRNA decay. We herein summarize the effects of several uORFs that regulate gene expression in microbes to illustrate the detailed mechanisms mediating uORF functions. Microbes are ideal for uORF studies because of their prompt responses to stimuli. Recent studies revealed uORFs are ubiquitous in higher eukaryotes. Moreover, they influence various physiological processes in mammalian cells by regulating gene expression, mostly at the translational level. Research conducted using rapidly evolving methods for ribosome profiling combined with protein analyses and computational annotations showed that uORFs in mammalian cells control gene expression similar to microbial uORFs, but they also have unique tumorigenesis-related roles because of their protein-encoding capacities. We briefly introduce cutting-edge research findings regarding uORFs in mammalian cells.
上游开放阅读框（uORFs）是下游基因表达的关键调控因子。具体而言，uORFs通过干扰翻译起始或介导mRNA降解来调节翻译。我们在此总结了几种调节微生物基因表达的uORFs的作用，以阐明介导uORF功能的详细机制。由于微生物对刺激反应迅速，因此它们是uORF研究的理想对象。最近的研究表明，uORFs在高等真核生物中普遍存在。此外，它们通过调节基因表达影响哺乳动物细胞中的各种生理过程，主要是在翻译水平。使用快速发展的核糖体谱分析方法结合蛋白质分析和计算注释进行的研究表明，哺乳动物细胞中的uORFs控制基因表达的方式与微生物uORFs相似，但由于它们的蛋白质编码能力，它们还具有独特的与肿瘤发生相关的作用。我们简要介绍了关于哺乳动物细胞中uORFs的前沿研究结果。
