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）：该提案概述了一项计划，将基因组数据分析、生物化学、结构生物学和功能表征结合起来，以了解核糖核蛋白复合物在调节 T 细胞激活中的作用。 挖掘表达数据以鉴定一组 RNA 结合蛋白，这些蛋白在 T 细胞激活时差异表达或选择性剪接。这些 RNA 结合蛋白构成了结构基因组学工作的输入，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从人类相互作用组数据库中鉴定出来，并且特定蛋白质-蛋白质复合物的形成将在 T 细胞和体外得到证实。由此产生的一组蛋白质-蛋白质复合物将作为第二目标流输入到结构基因组学工作中。 RNA 结合蛋白的 RNA 靶标将使用高通量测序和交联 (HITS-CLIP) 进行鉴定，并在 T 细胞和体外进行确认。由此产生的一组 RNA-蛋白质复合物将作为第三个目标流输入到结构基因组学工作中。对于结构基因组学工作中出现的蛋白质、蛋白质-蛋白质复合物和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。这项工作应该为结构提供重要的新见解 核糖核蛋白复合物的一般情况，以及对这些复合物如何参与的见解 转录后基因调控。