Liu Yue, Rao Shilpa, Hoskins Ian, Geng Michael, Zhao Qiuxia, Chacko Jonathan, Ghatpande Vighnesh, Qi Kangsheng, Persyn Logan, Wang Jun, Zheng Dinghai, Zhong Yochen, Park Dayea, Sarinay Cenik Elif, Agarwal Vikram, Ozadam Hakan, Cenik Can
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
mRNA Center of Excellence, Sanofi, Waltham, MA, USA.
Nat Biotechnol. 2025 Jul 25. doi: 10.1038/s41587-025-02718-5.
Characterizing shared patterns of RNA expression between genes across conditions has led to the discovery of regulatory networks and biological functions. However, it is unclear if such coordination extends to translation. In this study, we uniformly analyze 3,819 ribosome profiling datasets from 117 human and 94 mouse tissues and cell lines. We introduce the concept of translation efficiency covariation (TEC), identifying coordinated translation patterns across cell types. We nominate candidate mechanisms driving shared patterns of translation regulation. TEC is conserved across human and mouse cells and uncovers gene functions that are not evident from RNA or protein co-expression. Moreover, our observations indicate that proteins that physically interact are highly enriched for positive covariation at both translational and transcriptional levels. Our findings establish TEC as a conserved organizing principle of mammalian transcriptomes. TEC has potential as a predictive marker for gene function and may offer a framework for designing gene expression systems in synthetic biology and biotechnological applications.
对不同条件下基因间RNA表达的共享模式进行表征，已促成了调控网络和生物学功能的发现。然而，目前尚不清楚这种协同作用是否延伸至翻译过程。在本研究中，我们统一分析了来自117个人类和94个小鼠组织及细胞系的3819个核糖体谱数据集。我们引入了翻译效率共变（TEC）的概念，识别出跨细胞类型的协同翻译模式。我们提出了驱动翻译调控共享模式的候选机制。TEC在人类和小鼠细胞中是保守的，并且揭示了从RNA或蛋白质共表达中不明显的基因功能。此外，我们的观察结果表明，在翻译和转录水平上，发生物理相互作用的蛋白质在正共变方面高度富集。我们的发现确立了TEC作为哺乳动物转录组保守组织原则的地位。TEC有潜力作为基因功能的预测标志物，并可能为合成生物学和生物技术应用中设计基因表达系统提供一个框架。
