FUNCTIONS OF SMN - THE SPINAL MUSCULAR ATROPHY PROTEIN

SMN（脊髓性肌萎缩蛋白）的功能

• 批准号: 6540347
• 负责人: GIDEON DREYFUSS
• 金额: $ 30.3万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540347
• 关键词: HeLa cells; RNA binding protein; RNA splicing; X ray crystallography; Xenopus oocyte; complementary DNA; genetic library; immunocytochemistry; immunoprecipitation; in situ hybridization; laboratory rat; messenger RNA; molecular pathology; motor neurons; neural degeneration; progressive spinal muscular atrophy; protein protein interaction; protein structure function; small nuclear ribonucleoproteins; yeast two hybrid system

DESCRIPTION (Adapted from the Investigator's Abstract): Spinal Muscular Atrophy (SMA) is a common, devastating and often fatal motor neuron degenerative disease. SMA results from reduced levels of, or mutations in, the SMN (survival of motor neurons) protein. Work on the molecular characterization of the SMN protein led to the discovery of several of its functions, revealing novel cellular pathways and proteins. The investigators found that SMN is part of a complex that contains several proteins. All the components of the complex are novel proteins and they have already characterized several of them. Because they are tightly associated with SMN, the other proteins of the complex must be considered to be collaborators or modifiers of SMN function, and thus play a role in the course and severity of SMA. They also are candidate disease genes for other neuronal diseases. The SMN complex is expressed in all cells, but particularly high levels are found in neurons. It is present in both the cytoplasm and in the nucleus where it is concentrated in nuclear bodies, they termed gems. SMN functions in the biogenesis of snRNPs, the essential building blocks of the pre-mRNA splicing machinery, and in the pre-mRNA splicing process itself. Much remains to be learned about the structure, functions, and mechanism of action of SMN and the SMN complex. Studies will be carried out to understand in details the molecular functions and interactions of the SMN protein and of the SMN complex. From these studies approaches to therapy of SMA are likely to emerge.

描述（改编自研究者摘要）：脊髓性肌萎缩症 (SMA) 是一种常见的、具有破坏性且常常致命的运动神经元退行性病变 疾病。 SMA 是由 SMN（生存率）水平降低或突变引起的 运动神经元）蛋白质。 SMN的分子表征工作 蛋白质导致其多种功能的发现，揭示了新的 细胞途径和蛋白质。调查人员发现 SMN 是 含有多种蛋白质的复合物。该综合体的所有组成部分都是 新型蛋白质，他们已经对其中几种蛋白质进行了表征。因为 它们与 SMN 紧密相关，该复合物的其他蛋白质必须是 被认为是SMN功能的合作者或修饰者，从而发挥 SMA 的病程和严重程度中的作用。它们也是候选疾病基因 用于其他神经系统疾病。 SMN复合体在所有细胞中表达，但是 神经元中的含量特别高。它存在于两个 细胞质和细胞核中集中在核体中，它们 称为宝石。 SMN 在 snRNP 的生物合成中发挥作用，snRNP 是重要的构建体 前体 mRNA 剪接机制的模块以及前体 mRNA 剪接过程 本身。关于其结构、功能和功能还有很多需要了解的地方 SMN 和 SMN 复合物的作用机制。将进行研究 详细了解SMN的分子功能和相互作用 蛋白质和 SMN 复合物。从这些研究中得出 SMA 的治疗方法 都有可能出现。