Spliceosomal small nuclear ribonucleoproteins in trypanosomes: SMN-directed assembly of Sm core complexes and functional role of core variations

锥虫中的剪接体小核核糖核蛋白：SMN 指导的 Sm 核心复合物组装和核心变异的功能作用

• 批准号: 92423870
• 负责人: Professor Dr. Albrecht Bindereif
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/92423870?language=en
• 关键词: Spliceosomal; small; nuclear; ribonucleoproteins; trypanosomes

Spliceosomal small nuclear ribonucleoproteins (snRNPs) consist of a heteroheptameric ringlike Sm core assembled on the Sm binding site of the snRNA and additional, snRNP-specific proteins. Recently we have characterized the first examples of Sm core variations in the U2 and U4 snRNPs, where snRNP-specific Sm subunits replace two or one, respectively, of the canonical Sm subunits. In addition, we have identified the trypanosome SMN ortholog, and obtained initial functional evidence that it is involved in directing snRNA-specific Sm core assembly. Here we plan, first, to study the function of these core variations, focussing on the U4 snRNP. Second, we will biochemically analyze the mechanism of SMN-mediated Sm core assembly in the trypanosome system, using in vitro reconstitution and inducible RNAi knockdown systems. These studies promise new insights in the SMN function in a model, which appears to be much simpler than the multicomponent system of higher eukaryotes.

剪接体小核核糖核蛋白（snRNP）由在snRNA的Sm结合位点上组装的异七聚体环状Sm核心和另外的snRNP特异性蛋白组成。最近，我们的特点是第一个例子的Sm核心变化的U2和U4 snRNP，其中snRNP特异性Sm亚基取代两个或一个，分别是典型的Sm亚基。此外，我们已经确定了锥虫SMN直系同源物，并获得了初步的功能证据，它是参与指导snRNA特异性Sm核心组件。在这里，我们计划首先研究这些核心变体的功能，重点是U4 snRNP。第二，我们将生化分析的机制SMN介导的Sm核心组装在锥虫系统，使用体外重建和诱导RNAi敲低系统。这些研究有望在SMN功能的模型，这似乎是更简单的多组分系统的高等真核生物的新见解。