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，生化专门化的区域，通过以下方式彼此分开 膜是真核细胞的特征。这种细胞组织需要复杂的机制来 在适当的条件下，有效地将正确的大分子传递到正确的位置， 以及细胞器的生物发生、维持和遗传机制。我们的重点是 核。使用可用于我们的模型真核生物酵母酵母的遗传方法 我们之前鉴定出Loslp. cerevisiae。 Loslp 及其同源物 (Xpo-t) 在 tRNA 核中发挥作用 出口。然而，LOS^/Xpo-t 是所有生物体中的非必需基因，有可能消除其 功能，要求细胞具有不依赖Loslp的tRNA核输出途径。目标 1 拟议的工作采用候选技术和全基因组技术来揭示与 Loslp 无关的 tRNA 核输出途径。直到最近，tRNA 运动还被认为是单向的 核合成位点到胞质功能位点。然而我们发现反过来也 发生。事实上，从细胞质输入的大量 tRNA 会快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下。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。目标 2 试图了解控制逆行途径的机制及其与细胞的协调 代谢。在目标 3 中，我们采用全基因组方法来了解复杂和动态的 细胞核被组织成多个区域，这些区域之间没有被膜分开。迄今为止，我们 发现了 N-乙酰化的必要作用和一种完整的膜蛋白，以适当地束缚我们的 报告内核膜。我们寻求识别其他此类基因产物并了解是否 那些已经确定的在亚核组织中发挥一般作用。我们预计该信息 收集到的信息将在人类疾病方面具有重要应用，例如癌症、Emery-Dreifuss 肌肉疾病 营养不良和 Hutchison-Gilford 早衰综合征是由不适当的细胞核/细胞质引起的 动力学和核组织。