A comprehensive binding and functional map of human RNA-binding proteins

人类 RNA 结合蛋白的综合结合和功能图谱

• 批准号: 10687988
• 负责人: Brenton R. Graveley
• 金额: $ 139.02万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-05 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687988
• 关键词: Binding; Binding Proteins; Biology; Cells; Clinical; Collection; Communities; Complement; Data; Data Element; Data Set; Disease; Education; Education and Outreach; Elements; Encyclopedias; Etiology; Gene Expression; Genes; Genetic Diseases; Genetic Variation; Genomic approach; Goals; Human; Human Biology; Human Cell Line; Human Genome; Knock-out; Knowledge; Link; Maps; Measurement; Methods; Molecular; Molecular Profiling; Post-Transcriptional Regulation; Process; Production; Proteins; Public Health; RNA; RNA-Binding Proteins; RNA-Protein Interaction; Reagent; Reference Standards; Regulation; Reporting; Research; Resources; Role; Untranslated RNA; data portal; data repository; gene regulatory network; human disease; insight; knock-down; online resource; outreach; posttranscriptional; transcriptome; transcriptome sequencing; web interface

Project Summary The objective of the ENCORE (Encyclopedia of RNA Elements) project is to develop a foundational, functional map of protein-RNA interactions of RNA binding proteins (RBPs) encoded in the human genome, and the RNA elements they bind to across the transcriptome. These RNA elements, when expressed, form the basis of co- and post-transcriptional regulation of human genes. Our strategy consists of developing and integrating a physical map of 400 new RBPs in two different human cell lines with transcriptome-wide measurements of the effects of depleting these RBPs. Over the past 9 years, our group has established highly efficient data production workflows of experimental methods that will enable us to immediately expand these datasets further, which form a crucial and missing link to decipher the mechanisms of post-trancriptional regulation and how these impact genetic variation and disease etiology. When combined with the data we generated over the past 9 years, these efforts will culminate in a comprehensive map of the functional RNA elements recognized by essentially all RBPs expressed in two human cell lines, representing approximately half of the known complement of human RBPs. ENCORE will continue developing and integrating a physical map of hundreds of RBPs in two different human cell lines with transcriptome-wide measurements of the effects of depleting these RBPs. In addition, we will provide training and outreach to establish ENCORE annotations as the standard reference for co- and post-transcriptional research and clinical genomics efforts in the long-term. In summary, the data we will produce in this project will enable a more systematic and comprehensive understanding of the role of RBPs and RNA biology in the contribution to human biology and disease.

项目摘要 Encore的目的（RNA元素百科全书）项目是开发一个基础， 人类基因组中编码的RNA结合蛋白（RBP）蛋白RNA相互作用的功能图 以及它们在转录组中结合的RNA元素。这些RNA元素表达时形成 人类基因的共同转录调节的基础。我们的策略包括开发和 将400个新RBP的物理图与两种不同的人类细胞系中的物理图与整个转录组的范围 耗尽这些RBP的影响的测量。在过去的9年中，我们的小组已经建立了高度的 实验方法的有效数据生产工作流，这些方法将使我们能够立即扩展这些 进一步的数据集，形成了至关重要且缺失的链接，以破译循环后的机制 调节以及这些如何影响遗传变异和疾病病因。与数据结合使用时 在过去的9年中，这些效果将在功能性RNA的全面图中达到顶峰 本质上以两个人类细胞系表示的所有RBP识别的元素，大约表示 人类RBP的已知完成的一半。 Encore将继续开发和整合物理 在两个不同的人类细胞系中，具有数百个RBP的地图，并具有针对整个转录组的测量 耗尽这些RBP的影响。此外，我们将提供培训和外展 注释作为转录和后研究和临床基因组学的标准参考 从长远来看。总而言之，我们将在该项目中提供的数据将使更系统的和 对RBP和RNA生物学在对人类生物学贡献和RNA生物学的作用以及 疾病。