Integrated Resources to Elucidate RNA Sequence-Structure Relationships

阐明 RNA 序列-结构关系的综合资源

• 批准号: 9134849
• 负责人: NEOCLES B LEONTIS
• 金额: $ 31.55万
• 依托单位: BOWLING GREEN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-10 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134849
• 关键词: Advanced Development; Architecture; Atlases; Biological; Categories; Cell physiology; Cells; Cluster Analysis; Code; Communication; Complex; Consensus; Crystallography; Data; Diagnostic; Exhibits; Gene Expression; Genes; Genome; Goals; Grant; Human body; Imagery; Individual; Life; Ligand Binding; Ligands; Maps; Mediating; Methods; Molecular Conformation; Motion; Nucleic Acid Databases; Nucleotides; Organism; Physiological Processes; Play; Positioning Attribute; Protein Biosynthesis; Proteins; RNA; RNA Sequences; RNA-Protein Interaction; Research; Research Personnel; Resources; Role; Schedule; Sequence Alignment; Services; Signal Transduction; Source; Specificity; Structure; Structure-Activity Relationship; Untranslated RNA; Variant; base; data visualization; electron density; flexibility; genetic information; genome sequencing; improved; nano; protein complex; public health relevance; relational database; statistics; three dimensional structure; tool; web site

DESCRIPTION (provided by applicant): This is a continuation of a project to analyze, annotate, organize, and integrate RNA 3D structural data with RNA sequence and functional data and deliver it to biomedical researchers. The significance of the proposal lies in the prominent role of RNA, much of it non-protein-coding and structured, in a host of cellular and physiological processes, as revealed by recent high-throughput studies. Thousands of new non-coding RNAs have been discovered, many of which are expressed with temporal and spatial specificity. RNA plays many different roles in the human body, from carrying genetic information and regulating gene expression, to mediating intra-cellular communication, responding to environmental signals, and catalyzing important cellular processes such as protein synthesis. Deciphering the relationships between 3D structure and sequence is key to understanding RNA function. RNA 3D motifs are vital components in the architecture of RNA and in RNA- RNA and RNA-protein interactions. We are developing tools to study the variability of 3D motif structures across different conditions within the same and among homologous RNA molecules, integrating 3D structure and sequence data. These tools will be key to improving our ability to predict structure from sequence. The specific aims of the project are: 1. Deepen our understanding of RNA 3D structure by extracting and organizing 3D motifs. 2. Improve our understanding of the structural variation of RNA molecules and RNA complexes by examining and comparing 3D structures assigned to the same sequence/structure "equivalence" class. 3. Accelerate the study of the correspondence between RNA 3D structure and RNA sequence. 4. Provide annotations for RNA-protein interactions. 5. Develop new and extended tools for delivery, search and visualization of the RNA sequence and structure annotations. In the previous grant period, we created the RNA 3D Motif Atlas and a data pipeline to automatically extract, analyze and cluster RNA hairpin and internal loop motifs from new RNA-containing 3D structures on a monthly schedule; in the current project, we will do the same for RNA-RNA interaction motifs and RNA multi-helix junctions. We will use real-space refinement (RsR) statistics to evaluate, at the nucleotide level, how well RNA 3D structures fit the underlying experimental x-ray data. We will create and integrate annotations of RNA-protein interactions from a variety of resources; RNA- protein interactions are a key way that regulatory RNAs carry out their functions in living organisms. Finally, all products of the research will be made publicly available through the Nucleic Acid Database (NDB) website. These include interactive 2D maps and 3D visualizations of large RNAs, services to allow geometric searches for 3D structure fragments, and the many new annotations. These services will benefit a wide variety of biomedical researchers who will find ready access to what is known about the 3D structures of RNA motifs, interactions they make with other RNAs, interactions they make with proteins, and how to identify these through RNA sequence alone.

描述(申请人提供)：这是一个项目的延续，目的是分析、注释、组织和集成RNA 3D结构数据与RNA序列和功能数据，并将其交付给生物医学研究人员。该提议的意义在于，正如最近的高通量研究所揭示的那样，RNA在许多细胞和生理过程中发挥着突出的作用，其中大部分是非蛋白质编码的和结构化的。数以千计的新的非编码RNA已经被发现，其中许多表达具有时间和空间特异性。RNA在人体中扮演着许多不同的角色，从携带遗传信息和调节基因表达，到介导细胞内的交流，响应环境信号，以及催化蛋白质合成等重要的细胞过程。破译3D结构和序列之间的关系是理解RNA功能的关键。RNA3D基序是RNA结构以及RNA-RNA和RNA-蛋白质相互作用的重要组成部分。我们正在开发工具，以研究3D基序结构在不同条件下、相同RNA分子内和同源RNA分子之间的可变性，整合3D结构和序列数据。这些工具将是提高我们从序列预测结构的能力的关键。该项目的具体目标是：1.通过提取和组织3D模体来加深我们对RNA 3D结构的理解。2.通过检查和比较属于同一序列/结构“等价”类的三维结构，提高我们对RNA分子和RNA复合体结构变化的理解。3.加快研究RNA 3D结构与RNA序列的对应关系。4.为RNA-蛋白质相互作用提供注释。5.开发新的和扩展的工具，用于RNA序列和结构注释的交付、搜索和可视化。在上一个赠款期间，我们创建了RNA 3D基序图谱和一个数据管道，以每月从新的含RNA的3D结构中自动提取、分析和聚类RNA发夹和内部环基序；在当前项目中，我们将对RNA-RNA相互作用基序和RNA多螺旋连接做同样的工作。我们将使用实空间精化(RSR)统计数据在核苷酸水平上评估RNA3D结构与基本实验X射线数据的匹配程度。我们将创建和集成来自各种资源的RNA-蛋白质相互作用的注释；RNA-蛋白质相互作用是调节RNA在生物体内执行其功能的关键方式。最后，研究的所有产品将通过核酸数据库(NDB)网站公开提供。其中包括交互式2D地图和大型RNA的3D可视化，允许对3D结构片段进行几何搜索的服务，以及许多新的注释。这些服务将使各种各样的生物医学研究人员受益，他们将发现有关RNA基序的3D结构的已知信息，他们与其他RNA的相互作用，他们与蛋白质的相互作用，以及如何仅通过RNA序列来识别这些。