YEAST GENES IN RNA PROCESSING & NUCLEUS/CYTOSOL EXCHANGE

RNA 加工中的酵母基因

• 批准号: 7477593
• 负责人: Anita K Hopper
• 金额: $ 3.6万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-09-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7477593
• 关键词: Acetylation; Amino Acids; Area; Binding; Biochemical; Biogenesis; Biological; Carbohydrates; Cell Nucleus; Cells; Collection; Condition; Cytoplasm; Cytosol; Disease; Emery-Dreifuss Muscular Dystrophy; Enzymes; Essential Genes; Eukaryota; Eukaryotic Cell; Event; Excision; Family; Funding; Gene Expression; Genes; Genetic; Genome; Genomics; Glean; Grant; Growth; Homologous Gene; Human; Individual; Integral Membrane Protein; Introns; Learning; Location; Maintenance; Malignant Neoplasms; Membrane; Membrane Proteins; Metabolism; Modeling; Modification; Molecular; Movement; Nuclear; Nuclear Envelope; Nuclear Export; Nuclear Import; Nuclear Inner Membrane; Nuclear RNA; Nucleoplasm; Organelles; Organism; Pathway interactions; Physiological; Procedures; Process; Progeria; Protein Biosynthesis; Proteins; Proteome; RNA I; RNA Splicing; Regulation; Reporter; Role; Saccharomyces cerevisiae; Saccharomycetales; Signal Pathway; Site; Syndrome; Technology; Testing; Transcriptional Regulation; Transfer RNA; Translations; Work; Yeasts; crosslink; heterokaryon; human NAT2 protein; inorganic phosphate; macromolecule; member; mutant; tool

The presence of organelles, areas of biochemical specialization, separated from one another other by membranes characterize eukaryotic cells. Such cellular organization necessitates elaborate mechanisms to effectively deliver the correct macromolecules to the correct locations, under the appropriate conditions, as well as mechanisms for the biogenesis, maintenance and inheritance of the organelles. Our focus is on the nucleus. Using genetic approaches available for our model eukaryotic organism, yeast Saccharomyces cerevisiae we previously identified Loslp. Loslp and its homologues (Xpo-t) function in tRNA nuclear egress. However, LOS^/Xpo-t is an unessential gene in all organisms that it has been possible to ablate its function, requiring that cells possess Loslp-independent tRNA nuclear export pathway(s). Aim 1 of the proposed work employs both candidate and genome-wide technologies to uncover the Loslp-independent tRNA nuclear export pathway(s). Until recently tRNA movement was regarded to be unidirectional from the nuclear site of synthesis to the cytosolic site of function. However, we discovered that the reverse also occurs. In fact, large pools of tRNA imported from cytoplasm quickly and reversibly reside in the nucleus under particular physiological conditions or in particular yeast mutants. This "retrograde tRNA nuclear import pathway" is likely a newly discovered level of gene expression for all eukaryotic organisms. Aim 2 seeks to understand the mechanisms that govern the retrograde pathway and its coordination with cellular metabolism. In Aim 3 we employ genome-wide approaches to learn how the complicated and dynamic nucleus is organized into domains that are not separated from each other by membranes. To date, we discovered necessary roles for N-acetylation and an integral membrane protein to appropriately tether our reporter to the inner nuclear membrane. We seek to identify other such gene products and to learn whether those already identified fulfill general roles in subnuclear organization. We anticipate that the information gleaned will have significant application in human disorders, such as cancers, Emery-Dreifuss muscular dystrophy and Hutchison-Gilford Progeria syndrome that result from inappropriate nucleus/cytosol dynamics and nuclear organization.

细胞器的存在，生化专门化的领域，彼此之间通过 膜是真核细胞的特征。这种蜂窝组织需要复杂的机制来 在适当的条件下，将正确的大分子有效地输送到正确的位置，例如 以及细胞器的生物发生、维持和遗传机制。我们的重点是 原子核。使用可用于我们的真核生物模型--酵母--的遗传方法 Cerevisiae，我们之前鉴定为Loslp。Loslp及其同系物(XPO-t)在tRNA核中的作用 出口。然而，Los^/Xpo-t在所有生物体中都是一个不必要的基因，因此有可能去除它的 功能，要求细胞具有Loslp非依赖性tRNA核输出途径(S)。目标1 拟议的工作同时使用候选和全基因组技术来揭示Loslp非依赖性 核转录核糖核酸输出途径(S)。直到最近，tRNA的运动还被认为是单向的。 核部位的合成到胞浆部位的功能。然而，我们发现反之亦然。 发生。事实上，从细胞质输入的大量trna迅速且可逆地驻留在细胞核中。 在特定的生理条件下，或特别是酵母突变体。这种“逆行tRNA核” “输入途径”可能是所有真核生物新发现的基因表达水平。 试图了解支配逆行途径的机制及其与细胞的协调 新陈代谢。在目标3中，我们使用全基因组方法来了解复杂和动态的 核被组织成不被膜彼此分开的区域。迄今为止，我们 发现了N-乙酰化和一个完整的膜蛋白的必要作用，以适当地拴住我们的 记者向内核膜报告。我们试图鉴定其他类似的基因产物，并了解 那些已经确定的人在亚核组织中发挥一般作用。我们预计这些信息 Gleaned将在人类疾病中有重要的应用，如癌症、Emery-Dreifuss肌肉 核/胞浆不当所致的营养不良和Hutchison-Gilford Progeria综合征 动力学和核组织。