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（Encyclopedia of RNA Elements）Consortium的目标是： 开发RNA结合的蛋白质-RNA相互作用的基础功能图 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，形成了共同的基础。 和人类基因的转录后调控。我们的战略包括发展 并整合两种不同人类细胞系中300个RBP的物理图谱， 在转录组范围内测量消耗这些限制性商业惯例的影响， 定位模式及其与辅因子无关的结合偏好 协会.在过去的4年里，我们的财团（Burge，Graveley，Lecuyer和Yeo） 建立了高效的实验方法数据生产流程 (RNA bind-n-seq、RNA-seq、定位和增强型CLIP），这将使我们能够 立即扩展这些数据集，这些数据集形成了一个关键的和缺失的环节， 转录后调节机制以及这些机制如何影响遗传变异 和疾病病因学。结合我们过去四年的数据 这些努力将最终导致功能RNA的全面图谱 被两种人细胞系中表达的基本上所有RBP识别的元件， 代表了大约一半已知的人RBPs补体。ENCORE 将（1）产生并验证表达表位标记的 （2）开发这些RBP的转录组学和成像数据库， 简单的接口，供社区挖掘这一资源，（3）开发和分发 用于综合分析的工作流程和来自这些工作流程的可共享结果，以及（4） 提供培训和推广，将ENCORE注释确立为标准 共同和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