Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
ACS Chem Biol. 2023 Aug 18;18(8):1684-1697. doi: 10.1021/acschembio.3c00406. Epub 2023 Aug 4.
RNA plays a central role in biological processes, and its activity is regulated by a host of diverse chemical and biochemical mechanisms including post-transcriptional modification and interactions with RNA-binding proteins. Here, we describe our efforts to illuminate RNA biology through the application of chemical tools, focusing on post-transcriptional regulatory mechanisms. We describe the development of an activity-based protein profiling approach for discovery and characterization of RNA-modifying enzymes. Next, we highlight novel approaches for RNA imaging based upon metabolic labeling with modified nucleosides and engineering of the nucleotide salvage pathway. Finally, we discuss profiling RNA-protein interactions using small molecule-dependent RNA editing and synthetic photo-cross-linkable oligonucleotide probes. Our work provides enabling technologies for deciphering the complexity of RNA and its diverse functions in biology.
RNA 在生物过程中发挥着核心作用，其活性受到多种不同的化学和生化机制的调节，包括转录后修饰和与 RNA 结合蛋白的相互作用。在这里，我们描述了通过应用化学工具来阐明 RNA 生物学的努力，重点是转录后调节机制。我们描述了一种基于活性的蛋白质谱分析方法的开发，用于发现和表征 RNA 修饰酶。接下来，我们重点介绍了基于修饰核苷的代谢标记和核苷酸补救途径工程的新型 RNA 成像方法。最后，我们讨论了使用小分子依赖性 RNA 编辑和合成光交联寡核苷酸探针来分析 RNA-蛋白质相互作用。我们的工作为破译 RNA 的复杂性及其在生物学中的多种功能提供了使能技术。
