Exploring the Dynamic Structures of Nucleic Acids

人们日益认识到RNA的重要性，这为理解 它的动态结构如何在分子水平上对生物学做出贡献。核糖核酸的多功能性 源于其固有的构象灵活性和与广泛的 蜂窝伙伴。对RNA结构的评估受到支持的变异的挑战 这些多重角色。该方案支持紧耦合技术的继续应用 用于描述RNA结构系综的实验和计算工具。近期 进步提高了基于溶液的测量的分辨率或解释，揭示了 刚性元素的细微但重要的变化，如双层结构或全系列结构 由高度柔韧的未成对的股组成。该项目现在扩展了对RNA的研究 分离的基序到生物功能元件，目的是解析它们原子上的详细信息 工作方式。一个明显的焦点是单链基序的结构变化。抓获或 释放这些高度灵活的区域是一个有效的信号，它被用来调节 通过与离子、小配体或RNA基序的相互作用，如双链或 螺旋-连接-螺旋图案中的环。由于它们在控制基因表达方面的重要性， 这些主题为治疗干预或稳定现有的战略提供了新的目标 基于RNA的药物或疫苗。最后，这个项目将继续成功地努力刻画 柔性核酸基序与蛋白质的相互作用，为 了解大型核酸-蛋白质复合体是如何发挥作用的。

The increasing recognition of RNA’s importance provides strong motivation for understanding how its dynamic structures contribute to biology at the molecular scale. Much of RNA’s versatility is derived from its intrinsic conformational flexibility and capacity to interact with a broad range of cellular partners. Assessment of RNA’s structures is challenged by the variations that supports these multiple roles. This program supports the continued application of tightly coupled experimental and computational tools to characterize ensembles of RNA structures. Recent advances enhance the resolution or interpretation of solution-based measurements, revealing subtle but important changes in rigid elements, like duplexes, or the full range of structures assumed by highly flexible unpaired strands. This project now extends studies of RNA from isolated motifs to biologically functional elements and aims to resolve their atomically detailed workings. A distinct focus is on the structural variation of single-stranded motifs. The capture or release of these highly flexible regions is a potent signal exploited in regulating the translation of mRNAs into proteins, via interactions with ions, small ligands or RNA motifs such as duplexes or loops in helix-junction-helix motifs. Because of their importance in controlling gene expression, these motifs offer new targets for therapeutic intervention or strategies for stabilizing existing RNA-based drugs or vaccines. Finally, this project will continue successful efforts to characterize the interaction of flexible nucleic acid motifs with proteins, laying the groundwork for understanding how large nucleic acid-protein complexes function.