从静态结构到动态图景：冷冻电镜重新定义RNA生物学
From static structures to dynamic landscapes: cryo-EM redefines RNA biology
- Uppsala University（乌普萨拉大学）
- Istituto Italiano di Tecnologia（意大利理工学院）
- European Molecular Biology Laboratory (EMBL) Grenoble（欧洲分子生物学实验室（EMBL）格勒诺布尔分部）
机构由 AI 辅助整理，请以论文原文为准。
AI总结：
本文探讨冷冻电镜如何将RNA结构生物学研究从静态结构分析转向动态构象图景，通过8个案例展示其揭示RNA运动机制的作用，相关方法可解析构象变异性，还展望了其与其他技术结合的应用前景。
AI中文摘要：
RNA分子通过动态探索多种构象状态而非单一静态结构来发挥多样的生物学功能，捕获这些构象集合是分子生物学中的一项挑战。近期冷冻电镜（cryoEM）的进展正在改变这一局面，它能在近原子分辨率下可视化RNA分子在大量与功能相关的构象中的状态。本文探讨冷冻电镜如何重塑RNA结构生物学，将研究重点从静态结构分析转向动态构象图景。通过8个代表性案例研究，我们展示冷冻电镜如何揭示此前无法获取的RNA运动机制，包括折叠过程、配体依赖的转换及协同组装。我们专门讨论新兴的实验与计算方法，这些方法应对并克服了研究动态RNA时的挑战，尤其在构建设计、样品制备、玻璃化冷冻和数据分析方面。这些新方法可解析构象变异性，从冷冻电镜数据中重构离散与连续的RNA构象图景，凸显如何利用结构异质性提取功能见解。展望未来，冷冻电镜与互补生物物理技术及时间分辨方法的结合有望弥合结构与时间分辨率，常规获取RNA作用的实验分子电影。这些进展不仅将加深对RNA生物学的理解，还为RNA靶向疗法和动态RNA基纳米装置的合理设计提供新机遇。通过将结构快照连接为连贯的动态模型，冷冻电镜正在建立RNA能量图景及其功能作用的定量描述框架。
英文摘要：
RNA molecules perform diverse biological functions by dynamically exploring multiple conformational states rather than adopting a single static structure. Capturing these ensembles is a challenge in molecular biology. Recent advances in cryoEM are now transforming this landscape by enabling the visualization of RNA molecules across a broad spectrum of functionally relevant conformations at near atomic resolution. Here, we examine how cryoEM is reshaping RNA structural biology changing focus from the analysis of static structures to dynamic conformational landscapes. Through 8 representative case studies we illustrate how cryoEM has revealed previously inaccessible mechanisms of RNA motion, including folding processes, ligand-dependent switching, and cooperative assembly. We specifically discuss emerging experimental and computational approaches that address and overcome the challenges associated with studying dynamic RNAs, particularly in construct design, sample preparation, vitrification, and data analysis. These novel methods resolve conformational variability and enable the reconstruction of discrete and continuous RNA conformational landscapes from cryoEM data, highlighting how structural heterogeneity can be harnessed to extract functional insights. Looking forward, the integration of cryoEM with complementary biophysical techniques and time resolved methodologies promises to bridge structural and temporal resolution, to routinely derive experimental molecular movies of RNA in action. These advances will not only deepen our understanding of RNA biology but also provide new opportunities for RNA targeted therapeutics and the rational design of dynamic RNA-based nanodevices. By connecting structural snapshots into coherent dynamic models, cryoEM is establishing a framework for quantitative descriptions of RNA energy landscapes and their functional roles.
