Exploring the Dynamic Structures of Nucleic Acids

探索核酸的动态结构

• 批准号: 10330054
• 负责人: LOIS POLLACK
• 金额: $ 44万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10330054
• 关键词: Biological; Biology; Coupled; DNA; Disease; Drug Targeting; Elements; Gene Expression; Genes; Genetic Translation; Ions; Ligands; Malignant Neoplasms; Measurement; Modeling; Molecular Conformation; Motivation; Nucleic Acids; Pharmaceutical Preparations; Proteins; RNA; Resolution; Role; Signal Transduction; Structure; Techniques; Therapeutic Intervention; Vaccines; Variant; base; computerized tools; flexibility; insight; molecular scale; new therapeutic target; nucleic acid structure; programs; protein complex; targeted treatment

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.

人们对RNA重要性的日益认识为理解RNA提供了强大的动力。 它的动态结构如何在分子尺度上对生物学做出贡献。RNA的多功能性 是来自其内在的构象灵活性和能力，以相互作用的广泛的 细胞伙伴对RNA结构的评估受到了变异的挑战，这些变异支持了 这些多重角色。此程序支持紧耦合的 实验和计算工具来表征RNA结构的集合。最近 进步提高了分辨率或解释解决方案为基础的测量，揭示 刚性元素的微妙但重要的变化，如双胞胎，或全方位的结构 由高度灵活的不成对链构成。该项目现在将RNA的研究从 将孤立的基序转化为生物功能元件，旨在解决它们的原子细节问题。 工作。一个独特的重点是单链基序的结构变异。捕获或 这些高度灵活的区域的释放是一个强有力的信号，用于调节蛋白质的翻译。 mRNA通过与离子、小配体或RNA基序（如双链体或寡核苷酸）的相互作用转化为蛋白质。 螺旋-连接-螺旋基序中的环。由于它们在控制基因表达中的重要性， 这些基序为治疗干预提供了新的靶点， 基于RNA的药物或疫苗最后，该项目将继续成功的努力， 灵活的核酸基序与蛋白质的相互作用，奠定了基础 了解大型核酸-蛋白质复合物的功能。