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

项目概要 ENCORE（RNA 元素百科全书）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， 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 人类基因共转录和转录后调控的基础。我们的战略包括开发和 将两种不同人类细胞系中 400 个新 RBP 的物理图谱与全转录组整合 测量消耗这些 RBP 的影响。 9年来，我们集团已建立了高度 实验方法的高效数据生产工作流程将使我们能够立即扩展这些 进一步研究数据集，这形成了破译转录后机制的关键且缺失的环节 调控以及它们如何影响遗传变异和疾病病因。结合我们的数据 经过过去 9 年的努力，这些努力将最终形成功能性 RNA 的综合图谱 基本上所有在两个人类细胞系中表达的 RBP 都能识别的元件，大约代表 已知人类 RBP 补体的一半。 ENCORE 将继续开发和整合物理 两种不同人类细胞系中数百个 RBP 的图谱，以及全转录组测量 消耗这些 RBP 的影响。此外，我们将提供培训和推广，以建立 ENCORE 注释作为共转录和转录后研究以及临床基因组学工作的标准参考 从长远来看。总之，我们在这个项目中产生的数据将使我们能够更加系统和 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.