FUNCTIONS OF SMN - THE SPINAL MUSCULAR ATROPHY PROTEIN

SMN（脊髓性肌萎缩蛋白）的功能

• 批准号: 6394537
• 负责人: GIDEON DREYFUSS
• 金额: $ 30.34万
• 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 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394537
• 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）：脊髓性肌肉萎缩 (SMA)是一种常见的，毁灭性的，往往是致命的运动神经元退行性疾病， 疾病SMA是由SMN水平降低或SMN突变（生存率）引起的。 运动神经元）蛋白质。SMN的分子表征工作 蛋白质导致了它的几个功能的发现，揭示了新的 细胞通路和蛋白质。调查人员发现，SMN是一个 一种含有多种蛋白质的复合物。建筑群的所有组成部分都是 新的蛋白质，他们已经确定了其中几种蛋白质的特征。因为 它们与SMN紧密结合，复合物的其他蛋白质必须 被认为是SMN功能的合作者或修改者，从而发挥作用。 在SMA的病程和严重程度中的作用。它们也是候选疾病基因 治疗其他神经疾病SMN复合物在所有细胞中表达，但 在神经元中发现特别高的水平。它存在于两个 在细胞质和细胞核中，它集中在核体中， 称为宝石。SMN在snRNP的生物发生中起作用， 前体mRNA剪接机制的模块，并且在前体mRNA剪接过程中， 本身关于其结构、功能和 SMN和SMN复合物的作用机制。将开展研究， 详细了解SMN的分子功能和相互作用 蛋白质和SMN复合物。根据这些研究，SMA的治疗方法 很可能会出现。