A Comprehensive Functional Map of Human Protein-RNA Interactions

人类蛋白质-RNA 相互作用的综合功能图谱

• 批准号: 10087949
• 负责人: Brenton R. Graveley
• 金额: $ 226.97万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10087949
• 关键词: Affinity; Binding; Binding Sites; Biological Assay; Cell Line; Cells; Clinical; Collection; Communities; Complement; Data; Data Set; Databases; Education and Outreach; Elements; Encyclopedias; Ensure; Epitopes; Etiology; Foundations; Genes; Genetic Diseases; Genetic Transcription; Genetic Variation; Genomic approach; Goals; Human; Human Cell Line; Human Genome; Human Resources; Image; Immunofluorescence Immunologic; In Vitro; Knock-out; Knowledge; Link; Maps; Measurement; Methods; Pattern; Post-Transcriptional Regulation; Production; Public Health; RNA; RNA Binding; RNA Databases; RNA-Binding Proteins; RNA-Protein Interaction; Reference Standards; Regulation; Research; Research Personnel; Resources; Training; Untranslated RNA; base; insight; outreach; preference; stable cell line; transcriptome; transcriptome sequencing; transcriptomics

OVERALL – PROJECT SUMMARY The objective of the ENCORE (Encyclopedia of RNA Elements) Consortium 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 300 RBPs in two different human cell lines with transcriptome-wide measurements of the effects of depleting these RBPs, their localization patterns and their binding preferences independent of co-factor associations. Over the past 4 years, our consortium (Burge, Graveley, Lecuyer and Yeo) has established highly efficient data production workflows of experimental methods (RNA bind-n-seq, RNA-seq, Localization and enhanced CLIP) that will enable us to immediately expand these datasets, 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 four 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 (1) generate and validate a physical resource of cell lines expressing epitope-tagged RBPs, (2) develop transcriptomics and imaging databases of these RBPs to provide simple interfaces for the community to mine this resource, (3) develop and distribute workflows for integrative analyses and shareable results from these workflows and (4) 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.

总体 - 项目摘要 Encore（RNA元素百科全书）的目的是 开发RNA结合的蛋白RNA相互作用的基础功能图 在人基因组中编码的蛋白质（RBP）及其结合的RNA元素 跨转录组。这些RNA元素在表达时构成了共同的基础 和人类基因的转录后调节。我们的策略包括发展 并在两个不同的人类细胞系中集成了300个RBP的物理图 耗尽这些RBP的影响的全转录组的测量值 本地化模式及其结合偏好独立于共同因素 协会。在过去的四年中，我们的财团（Burge，Graveley，Lecuyer和Yeo） 已经建立了实验方法的高效数据生产工作流程 （RNA结合-N-Seq，RNA-Seq，定位和增强夹）将使我们能够 立即扩展这些数据集，这些数据集形成了与破译的关键和缺失的链接 转录后调节的机制以及这些机制如何影响遗传变异 和疾病病因。当与过去四个的数据结合使用时 多年来，这些努力将在功能性RNA的全面图中达到顶峰 本质上所有RBP识别的元素在两个人类细胞系中表达， 大约是人类RBP的已知完成的一半。 encore 将（1）生成和验证表达表位标记的细胞系的物理资源 RBP，（2）开发这些RBP的转录组学和成像数据库以提供 社区挖掘此资源的简单接口，（3）开发和分发 这些工作流的集成分析和可共享结果的工作流以及（4） 提供培训和宣传，以建立连续注释作为标准 参考转录和后后研究和临床基因组学的参考 长期。

项目成果

RBP Image Database: A resource for the systematic characterization of the subcellular distribution properties of human RNA binding proteins.

• DOI: 10.1093/nar/gkac971
• 发表时间: 2023-01-06
• 期刊: NUCLEIC ACIDS RESEARCH
• 影响因子: 14.9
• 作者: Bouvrette, Louis Philip Benoit;Wang, Xiaofeng;Boulais, Jonathan;Kong, Jian;Syed, Easin Uddin;Blue, Steven M.;Zhan, Lijun;Olson, Sara;Stanton, Rebecca;Wei, Xintao;Yee, Brian;Van Nostrand, Eric L.;Fu, Xiang-Dong;Burge, Christopher B.;Graveley, Brenton R.;Yeo, Gene W.;Lecuyer, Eric
• 通讯作者: Lecuyer, Eric

Metadensity: a background-aware python pipeline for summarizing CLIP signals on various transcriptomic sites.

• DOI: 10.1093/bioadv/vbac083
• 发表时间: 2022
• 期刊: Bioinformatics advances

ADAR and hnRNPC deficiency synergize in activating endogenous dsRNA-induced type I IFN responses.

• DOI: 10.1084/jem.20201833
• 发表时间: 2021-09-06
• 期刊: The Journal of experimental medicine
• 作者: Herzner AM;Khan Z;Van Nostrand EL;Chan S;Cuellar T;Chen R;Pechuan-Jorge X;Komuves L;Solon M;Modrusan Z;Haley B;Yeo GW;Behrens TW;Albert ML
• 通讯作者: Albert ML