YEAST GENES IN RNA PROCESSING & NUCLEUS/CYTOSOL EXCHANGE

RNA 加工中的酵母基因

• 批准号: 7148140
• 负责人: Anita K Hopper
• 金额: $ 23.5万
• 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/7148140
• 关键词: RNA splicing; Saccharomyces cerevisiae; acetylation; acyltransferase; aminoacid metabolism; biological signal transduction; carbohydrate metabolism; cell nucleus; cytoplasm; enzyme activity; fungal genetics; gene expression; gene mutation; genetic regulation; green fluorescent proteins; heterokaryon; intracellular transport; introns; membrane proteins; nuclear membrane; posttranscriptional RNA processing; protein biosynthesis; protein structure function; transfer RNA

DESCRIPTION (provided by applicant): 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 Los1p. Los1p and its homologues (Xpo-t) function in tRNA nuclear egress. However, LOS1/Xpo-t is an unessential gene in all organisms that it has been possible to ablate its function, requiring that cells possess Los1p-independent tRNA nuclear export pathway(s). Aim 1 of the proposed work employs both candidate and genome-wide technologies to uncover the Los1p-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.

描述（由申请人提供）：细胞器的存在，生化专业的区域，由膜彼此隔开，表征了真核细胞。这种细胞组织需要精心的机制在适当的条件下向正确的位置有效地将正确的大分子传递到了细胞器的生物发生，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学方法，酿酒酵母酵母糖酵母我们先前鉴定出LOS1P。 LOS1P及其同源物（XPO-T）在tRNA核出口中的功能。然而，LOS1/XPO-T是所有生物体中可以消除其功能的无用基因，要求细胞具有LOS1P独立的TRNA核出口途径（S）。拟议工作的目标1采用候选和全基因组技术来揭示非LOS1P独立的tRNA核出口途径（S）。直到最近，tRNA运动被认为是从合成的核位点到功能的胞质部位的单向。但是，我们发现相反也发生。实际上，在特定的生理条件下，尤其是酵母突变体，从细胞质进口的大量tRNA迅速而可逆地驻留在核中。这种“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。 AIM 2试图了解控制逆行途径的机制及其与细胞代谢的协调。在AIM 3中，我们采用全基因组方法来了解如何将复杂和动态核组织到不被膜分开的域。迄今为止，我们发现了N-乙酰化的必要作用和整体膜蛋白适当地将记者绑在内部核膜上。我们试图确定其他此类基因产品，并了解那些已经确定已经在亚核组织中扮演的一般角色的人。我们预计，收集的信息将在人类疾病中具有重大应用，例如癌症，emery-dreifuss肌肉营养不良症和hutchison-gilford型后代综合征，这些综合征是由不适当的细胞核/细胞质动力学和核组织而导致的。