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)联盟的目标是 开发RNA结合的蛋白质-RNA相互作用的基础性、功能性地图 人类基因组中编码的蛋白质(RBP)及其结合的RNA元件 在转录组中。这些RNA元件，当表达时，形成了co- 以及人类基因的转录后调控。我们的战略包括发展 将两个不同的人类细胞系中的300个限制性商业惯例的物理图谱与 对耗尽这些限制性商业惯例的影响的转录组范围的测量，他们的 独立于共因子的局部化模式及其绑定偏好 联想。在过去的4年里，我们的财团(Burge，Graveley，Lecuyer和Yeo) 建立了高效的数据生产工作流程的实验方法 (RNA绑定-n-seq、RNA-seq、本地化和增强型剪辑)，使我们能够 立即扩展这些数据集，它们构成了破译的关键和缺失的一环 转录后调控机制及其对遗传变异的影响 和疾病病因学。与我们在过去四年中生成的数据相结合 几年后，这些努力将最终形成一张功能RNA的全面图谱 在两个人类细胞系中表达的基本上所有限制性商业惯例都能识别的元件， 约占人类限制性商业惯例已知补充量的一半。再来一次 将(1)生成并验证表达表位标记的细胞系的物理资源 限制性商业惯例，(2)开发这些限制性商业惯例的转录和成像数据库，以提供 为社区开发和分发此资源提供了简单的界面 用于综合分析的工作流和来自这些工作流的共享结果以及(4) 提供培训和推广，以建立安可注解作为标准 联合转录后研究和临床基因组学工作的参考 长期的。

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