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

项目摘要 ENCORE（Encyclopedia of RNA Elements）项目的目标是开发一个基础的， 人类基因组中编码的RNA结合蛋白（RBP）的蛋白质-RNA相互作用的功能图谱， 以及它们在转录组中结合的RNA元件。这些RNA元件在表达时形成 人类基因的共转录和转录后调控的基础。我们的战略包括发展和 在两个不同的人类细胞系中整合400个新RBP的物理图谱， 测量消耗这些限制性商业惯例的效果。在过去的9年里，我们的集团已经建立了高度 有效的数据生产工作展示了实验方法，使我们能够立即扩大这些 数据集进一步，这形成了一个关键的和缺失的环节，以破译转录后的机制， 调控以及这些调控如何影响遗传变异和疾病病因。当结合数据时， 在过去9年中产生的，这些成果将最终在功能RNA的全面地图 在两种人细胞系中表达的基本上所有RBP识别的元件，代表大约 已知人类RBPs补体的一半。ENCORE将继续开发和整合一个物理 两种不同人类细胞系中数百种RBP的图谱， 消除这些限制性商业惯例的效果。此外，我们将提供培训和推广，以建立ENCORE 注释作为共同和转录后研究和临床基因组学研究的标准参考 从长远来看总之，我们将在本项目中产生的数据将使一个更系统， 全面了解RBP和RNA生物学对人类生物学的贡献， 疾病

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.