Nuclear Organization of RNA Polymerase III Transcription

RNA 聚合酶 III 转录的核组织

基本信息

批准号：
8063228
负责人：
DAVID R ENGELKE
金额：
$ 29.34万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8063228
关键词：
7SL RNA Adverse effects Affect Alu Elements Area Behavior Beryllium Binding Cell Cycle Cell Nucleolus Cell Nucleus Cells Chromosome Mapping Chromosomes Chromosomes, Human, Pair 16 Complex DNA DNA Packaging DNA Polymerase II DNA Repair Development Elements Employee Strikes Environment Enzymes Eukaryota Event Fungal Genome Gene Cluster Gene Order Genes Genetic Genetic Recombination Genetic Transcription Genome Goals Human Human Genome In Vitro Indium Individual Lead Life Malignant Neoplasms Mammalian Cell Mammals Maps Mediating Metabolic Microtubules Mitotic Chromosome Molecular Molecular Genetics Mus Nature Nuclear Pathway interactions Physical condensation Polymerase Process Proteins RNA Polymerase II RNA Polymerase III RNA Processing Regulation Research Resolution Retrieval Retrotransposon Role Saccharomyces cerevisiae Saccharomycetales Signal Transduction Site Small RNA Spatial Behavior Staging Tandem Repeat Sequences Testing Transcriptional Regulation Transfer RNA Vertebrates Yeasts chromatin immunoprecipitation condensin in vivo insight mutant promoter protein complex public health relevance rRNA Genes research study response segregation tRNA Precursor tool ultra high resolution vertebrate genome

项目摘要

DESCRIPTION (provided by applicant): Genetic information is usually represented as linear arrays on chromosomes, yet nuclear DNA exists in a highly compacted form in which access to individual genes must be considered as a three-dimensional problem. Cytological evidence for a limited number of loci in several eukaryotes has suggested that localization of at least some genes is related to the transcriptional activity of the genes, and that this positioning can change in response to metabolic and developmental signals. Using the budding yeast, Saccharomyces cerevisiae, we have recently shown that the 275 tRNA genes, although widely scattered in the linear genome, are gathered near the nucleolus throughout the cell cycle. This clustering of the tRNA genes, while potentially advantageous in terms of RNA polymerase III (pol III) transcriptional regulation and an ordered pre-Trna processing pathway, has striking implications for spatial organization of much of the yeast genome. The clustering is pol III transcription-dependent, and affects both recombinations between tRNA genes and nearby transcription by RNA polymerase II. In preliminary studies we have now shown that nucleolar tRNA gene localization is a two step process, with condensin-dependent clustering of the tRNA genes separable from microtubule-dependent localization of the clusters to the nucleolus. The near-term goal of this project is to characterize the mechanisms of this large-scale organization of the individual tRNA genes in yeast, to take advantage of the molecular genetic tools. In the longer term we will also investigate whether this phenomenon affects the behavior of RNA polymerase III transcription units in mammals. Genomes from humans and other vertebrates contain not only hundreds of tRNA genes, but hundreds of thousands of short interspersed DNA elements (SINEs) with tRNA-class promoters. Some of these short interspersed DNA elements (SINEs) are known to influence both nearby transcription by RNA polymerase II and recombination events that are associated with developmental abnormalities and cancers. We anticipate that understanding the spatial behavior of pol III transcription units could provide broad insights into constraints on genome organization and regulation. PUBLIC HEALTH RELEVANCE: DNA in living cells is extremely condensed and packaged in a highly organized fashion. This packaging facilitates regulated retrieval of genetic information and affects DNA recombination events that can lead to cancers and developmental abnormalities. We have identified a type of abundant DNA element, distributed throughout genomes of higher cells, that both encodes small RNAs and serves as a three-dimensional organization signal. We are investigating the molecular mechanisms of this organization and the nature of the resulting DNA packaging.

描述（由申请人提供）：遗传信息通常表示为染色体上的线性阵列，但是核DNA以高度紧凑的形式存在，其中必须将访问单个基因的访问视为三维问题。几个真核生物中数量有限的基因座的细胞学证据表明，至少某些基因的定位与基因的转录活性有关，并且这种定位可以改变对代谢和发育信号的响应。使用酿酒酵母的芽酵母，我们最近表明，在整个细胞周期中，275个tRNA基因虽然广泛散布在线性基因组中，但在核仁附近收集。 TRNA基因的这种聚类虽然在RNA聚合酶III（POLII）（POLII）转录调控和有序的前TRNA处理途径方面具有有利的影响，但对许多酵母基因组的空间组织具有显着意义。聚类是POL III转录依赖性的，并且会影响TRNA基因和RNA聚合酶II附近转录之间的重组。在初步研究中，我们现在表明核仁tRNA基因定位是一个两步过程，condensin依赖性的tRNA基因依赖性聚类可与簇的微管依赖性定位分离到核仁。该项目的近期目标是表征酵母中单个tRNA基因的大规模组织的机制，以利用分子遗传工具。从长远来看，我们还将研究这种现象是否影响哺乳动物中RNA聚合酶III转录单元的行为。来自人类和其他脊椎动物的基因组不仅包含数百个tRNA基因，还包含数十万个短散布的DNA元素（SINES）与tRNA级启动子。这些简短的散布的DNA元素（SINES）中的一些会影响RNA聚合酶II的附近转录，以及与发育异常和癌症相关的重组事件。我们预计，了解Pol III转录单元的空间行为可以为对基因组组织和调节的限制提供广泛的见解。公共卫生相关性：活细胞中的DNA极度凝结和包装，以高度有条理的方式包装。这种包装有助于调节遗传信息的检索，并影响DNA重组事件，这可能导致癌症和发育异常。我们已经确定了一种分布在较高细胞的基因组中的丰富DNA元素，它们均编码小RNA，并且用作三维组织信号。我们正在研究该组织的分子机制以及所得的DNA包装的性质。