Regulatory mechanisms in the recycling phase of the spliceosome cycle: combining the human and zebrafish systems

剪接体循环回收阶段的调节机制：结合人类和斑马鱼系统

• 批准号: 105594369
• 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 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/105594369?language=en
• 关键词: Regulatory; mechanisms; recycling; phase; spliceosome

Nuclear pre-mRNA splicing requires more than 100 protein factors as well as five small nuclear RNAs (snRNAs), which cooperate in the three stages of the spliceosome cycle: assembly, splicing catalysis, and recycling. Here we focus on the recycling phase, specifically on the protein factor p110, which is required for efficient U4/U6 snRNP recycling and which we have identified and previously characterized both in the human and zebrafish systems. We will use a combination of the human and zebrafish systems, thereby further establishing zebrafish as a valuable new model system in the splicing field. Specific aims are, first, to investigate the contributions of p110 and the LSm proteins in U4/U6 snRNP recycling; second, to identify genes and splicing targets affected by p110 deficiency; third, to characterize the network of coregulated components of the recycling phase; and fourth, to identify new recycling factors. In sum, this project addresses not only the mechanistic and regulatory aspects of snRNP recycling, but also the important question of how defects in a general splicing factor can result in very specific phenotypes, which is relevant for our molecular understanding of human disease.

核pre-mRNA剪接需要100多种蛋白质因子和5种小核rna (snrna)，它们在剪接体周期的三个阶段：组装、剪接催化和再循环中相互配合。在这里，我们专注于回收阶段，特别是蛋白质因子p110，这是有效的U4/U6 snRNP回收所必需的，我们已经在人类和斑马鱼系统中发现并表征了它。我们将使用人类和斑马鱼系统的结合，从而进一步建立斑马鱼作为剪接领域有价值的新模型系统。具体目标是：首先，研究p110和LSm蛋白在U4/U6 snRNP循环中的作用；二是鉴定受p110缺乏影响的基因和剪接靶点；第三，表征回收阶段的共调节组分网络；第四，确定新的回收因素。总之，该项目不仅解决了snRNP循环的机制和调控方面的问题，而且还解决了一般剪接因子中的缺陷如何导致非常特定的表型的重要问题，这与我们对人类疾病的分子理解有关。