Ribonucleoprotein Complexes Regulating T-Cell Activation

调节 T 细胞激活的核糖核蛋白复合物

• 批准号: 8152103
• 负责人: Daniel R. Salomon
• 金额: $ 125.15万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8152103
• 关键词: Ribonucleoprotein; Complexes; Regulating; Cell; Activation

DESCRIPTION (provided by applicant): This proposal outlines a plan to combine genomic data analysis, biochemistry, structural biology, and functional characterization to understand the role of ribonucleoprotein complexes in regulating T-cell activation. Expression data were mined to identify a set of RNA-binding proteins that were either differentially expressed or alternatively spliced, upon T-cell activation. These RNA-binding proteins constitute the input into a structural genomics effort, representing the first of three structural target streams. Protein interacting partners for these RNA-binding proteins have been identified from the Human Interactome Database, and the formation of specific protein-protein complexes will be confirmed both in T-cells and in vitro. The resulting set of protein-protein complexes will be input into a structural genomics effort as the second target stream. The RNA targets for the RNA-binding proteins will be identified using high throughput sequencing and crosslinking (HITS-CLIP), and confirmed in T-cells and in vitro. The resulting set of RNA-protein complexes will be input into a structural genomics effort as the third target stream. For the proteins, protein-protein complexes, and RNA-protein complexes that emerge from the structural genomics effort, functional validation will be carried out in T-cells to determine the role of these specific components in T-cell activation. This work should provide significant new insights into the structure of ribonucleoprotein complexes in general, as well as insights into how these complexes are involved in posttranscriptional gene regulation.

描述（由申请人提供）：该提案概述了结合基因组数据分析，生物化学，结构生物学和功能表征的计划，以了解核糖核蛋白复合物在调节T细胞激活中的作用。 挖掘表达数据以识别一组在T细胞激活后差异表达或剪接的RNA结合蛋白。这些RNA结合蛋白构成了结构性基因组学努力的输入，代表了三个结构目标流中的第一个。这些RNA结合蛋白的蛋白质相互作用伙伴已经从人类相互作用组数据库中鉴定出来，并且在T细胞和体外都将确认特定蛋白质 - 蛋白质复合物的形成。所得的蛋白质 - 蛋白质复合物集将作为第二个靶流量输入结构基因组学。将使用高吞吐量测序和交联（hits-CLIP）鉴定RNA结合蛋白的RNA靶标，并在T细胞和体外确认。由此产生的RNA蛋白质复合物将被输入到结构基因组学工作中，作为第三个目标流。对于蛋白质，蛋白质 - 蛋白质复合物和从结构基因组学努力中产生的RNA-蛋白质复合物，将在T细胞中进行功能验证，以确定这些特定成分在T细胞激活中的作用。这项工作应为结构提供重大新见解 一般而言的核糖核蛋白蛋白复合物以及对这些复合物如何参与的见解 转录后基因调控。