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，生化专业领域，彼此之间的分离 膜表征真核细胞。这样的细胞组织需要详尽的机制 在适当条件下，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，维持和遗传的机制。我们的重点是 核。使用用于我们模型的真核生物的遗传方法，酵母糖疗法 酿酒酵母我们先前鉴定出LOSLP。 LOSLP及其同源物（XPO-T）在tRNA核中的功能 出口。但是，los^/xpo-t是所有生物体中的不必要基因 功能，要求细胞具有非依赖LOSLP的tRNA核输出途径（S）。目标1 拟议的工作既采用候选者和全基因组技术 tRNA核出口途径。直到最近，tRNA运动被认为是单向的 合成与功能的胞质位点的核位点。但是，我们发现相反 发生。实际上，从细胞质中进口的大量tRNA迅速而可逆地驻留在细胞核中 在特定的生理条件下，特别是酵母突变体。这个“逆行tRNA核 进口途径”可能是所有真核生物的新发现的基因表达水平。 试图了解控制逆行途径的机制及其与细胞的协调 代谢。在AIM 3中，我们采用全基因组方法来学习如何复杂和动态 细胞核被组织成没有被膜分开的结构域。迄今为止，我们 发现了N-乙酰化和整体膜蛋白的必要作用 内部核膜的记者。我们试图识别其他此类基因产品，并了解是否 那些已经确定在亚核组织中扮演的一般角色的人。我们预计这些信息 收集的将在人类疾病中有重大应用 不适当核/细胞质导致的营养不良和记结-Gilford综合征 动态和核组织。