Integrated Resources to Elucidate RNA Sequence-Structure Relationships

描述（由申请人提供）：这是一个项目的延续，分析、注释、组织和整合RNA 3D结构数据与RNA序列和功能数据，并将其提供给生物医学研究人员。最近的高通量研究表明，这一提议的意义在于RNA在许多细胞和生理过程中的突出作用，其中大部分是非蛋白质编码和结构化的。已经发现了数千种新的非编码rna，其中许多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，到介导细胞内通讯，响应环境信号，以及催化重要的细胞过程，如蛋白质合成。破译三维结构和序列之间的关系是理解RNA功能的关键。RNA三维基序是RNA结构、RNA- RNA和RNA-蛋白相互作用的重要组成部分。我们正在开发工具来研究相同和同源RNA分子内不同条件下3D基序结构的变异性，整合3D结构和序列数据。这些工具将是提高我们从序列中预测结构能力的关键。该项目的具体目标是：1。通过提取和组织3D基序，加深我们对RNA 3D结构的理解。2. 通过检查和比较分配给相同序列/结构“等效”类的3D结构，提高我们对RNA分子和RNA复合物结构变化的理解。3. 加快研究RNA三维结构与RNA序列的对应关系。4. 提供rna -蛋白相互作用的注释。5. 开发新的和扩展的工具，用于RNA序列和结构注释的传递，搜索和可视化。在之前的资助期间，我们创建了RNA 3D Motif Atlas和一个数据管道，以自动提取，分析和聚类RNA发夹和内部环基序，从新的含有RNA的3D结构每月一次；在目前的项目中，我们将对RNA-RNA相互作用基序和RNA多螺旋连接进行同样的研究。我们将使用实空间细化（RsR）统计来评估，在核苷酸水平上，RNA 3D结构与基础实验x射线数据的匹配程度。我们将从各种资源中创建和整合rna -蛋白质相互作用的注释；RNA-蛋白相互作用是调控RNA在生物体中发挥作用的关键途径。最后，所有研究成果将通过核酸数据库（NDB）网站公开。其中包括大型rna的交互式2D地图和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，他们将找到现成的途径来了解RNA基序的3D结构，它们与其他RNA的相互作用，它们与蛋白质的相互作用，以及如何通过RNA序列单独识别这些结构。

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.