Genetics and Biochemistry of Ribosome Synthesis

核糖体合成的遗传学和生物化学

基本信息

  • 批准号:
    7905744
  • 负责人:
  • 金额:
    $ 32.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-08-31 至 2011-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The ribosome, the central machinery essential for protein synthesis, obviously plays a key role in cell growth and its synthesis is intimately connected to the regulation of cell proliferation. Indeed, recent studies suggest important roles for regulation of ribosome synthesis in the development and growth of tumor cells. Our goal is to understand how cells regulate the production of ribosomes in response to environmental conditions. Since transcription of ribosomal RNA (rRNA) is central in determining overall synthesis of ribosomes, our work focuses on regulation of rRNA synthesis by RNA Polymerase I (Pol I). We use the yeast Saccharomyces cerevisiae as a model system because of the ease of genetic manipulation and the available knowledge of rRNA synthesis by RNA polymerase I. Previous studies showed that yeast cells change rRNA synthesis rate by two mechanisms. One is by altering the number of active (open) genes, and another is by altering the activity of individual active genes. In the past, we concentrated on studies of mechanisms of initiation of transcription at individual active genes. Although we will continue this line of work, more emphasis will now be given to studies of post-initiation steps and its regulation at individual active genes. It is now known that rRNA modification, processing and some of assembly reactions take place co-transcriptionally. Therefore, it is likely that transcription and processing/assembly of rRNA are coupled and co-regulated. We have recently identified that mutational defects in the Spt4/5 complex, a known elongation factor for mRNA transcription, cause defects in elongation of Pol I. We plan to identify regions within the rRNA gene that require this factor for their transcription and study roles played by this factor using genetic and biochemical approaches. We will isolate mutants with specific defects in Pol I transcription elongation steps. We are especially interested in those mutants with defects in coupling of transcription with rRNA processing/assembly. In relation to this goal, we have unpublished observations showing an apparent dependence of 18S rRNA synthesis (and/or 40S subunit assembly) on 5.8S-25S rRNA synthesis (and/or 60S subunit assembly). We plan to determine whether 18S rRNA transcription itself, rather than 40S subunit assembly, is dependent on 5.8S-25S rRNA transcription (and/or 40S subunit assembly), and then to study the mechanism involved. Finally, we plan to study the mechanism that controls switching between active and inactive states of rRNA genes. We will compare RNA and protein components associated with active genes with those associated with inactive genes in order to build an understanding of the mechanism involved in switching. We also plan to isolate mutants defective in switching and study these mutants to identify the mechanism. We expect that the proposed work will make significant contributions to our understanding of transcription of rRNA genes and its regulation.
描述(由申请人提供):核糖体是蛋白质合成的核心机制,在细胞生长中起着关键作用,其合成与细胞增殖的调节密切相关。事实上,最近的研究表明核糖体合成在肿瘤细胞的发育和生长中起着重要的调节作用。我们的目标是了解细胞如何根据环境条件调节核糖体的产生。由于核糖体RNA (rRNA)的转录是决定核糖体整体合成的核心,我们的工作重点是RNA聚合酶I (Pol I)对rRNA合成的调控。我们选择酵母酵母作为模型系统,是因为易于遗传操作和现有的RNA聚合酶合成rRNA的知识。先前的研究表明,酵母细胞通过两种机制改变rRNA的合成速率。一种是通过改变活跃(开放)基因的数量,另一种是通过改变单个活跃基因的活性。过去,我们主要研究单个活性基因的转录起始机制。虽然我们将继续这项工作,但现在更多的重点将放在研究起始后的步骤及其对单个活性基因的调节上。现在已经知道,rRNA修饰、加工和一些组装反应是共转录发生的。因此,rRNA的转录和加工/组装可能是耦合和共同调控的。我们最近发现Spt4/5复合物(一种已知的mRNA转录延伸因子)的突变缺陷会导致Pol i的延伸缺陷。我们计划在rRNA基因中确定需要该因子进行转录的区域,并使用遗传和生化方法研究该因子所起的作用。我们将分离在Pol I转录延伸步骤中具有特定缺陷的突变体。我们对那些在转录与rRNA加工/组装耦合方面存在缺陷的突变体特别感兴趣。关于这一目标,我们有未发表的观察结果显示,18S rRNA合成(和/或40S亚基组装)明显依赖于5.8S-25S rRNA合成(和/或60S亚基组装)。我们计划确定18S rRNA转录本身,而不是40S亚基组装,是否依赖于5.8S-25S rRNA转录(和/或40S亚基组装),然后研究其中的机制。最后,我们计划研究控制rRNA基因在活性和非活性状态之间切换的机制。我们将比较与活性基因相关的RNA和蛋白质成分与与非活性基因相关的RNA和蛋白质成分,以建立对开关机制的理解。我们还计划分离开关缺陷突变体并研究这些突变体以确定其机制。我们期望所提出的工作将对我们对rRNA基因转录及其调控的理解做出重大贡献。

项目成果

期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Isolation and characterization of temperature-sensitive mutations in RPA190, the gene encoding the largest subunit of RNA polymerase I from Saccharomyces cerevisiae.
RPA190 温度敏感突变的分离和表征,RPA190 是编码酿酒酵母 RNA 聚合酶 I 最大亚基的基因。
  • DOI:
    10.1128/mcb.8.10.3997-4008.1988
  • 发表时间:
    1988
  • 期刊:
  • 影响因子:
    5.3
  • 作者:
    Wittekind,M;Dodd,J;Vu,L;Kolb,JM;Buhler,JM;Sentenac,A;Nomura,M
  • 通讯作者:
    Nomura,M
Deficiency in both type I and type II DNA topoisomerase activities differentially affect rRNA and ribosomal protein synthesis in Schizosaccharomyces pombe.
I 型和 II 型 DNA 拓扑异构酶活性的缺陷对粟酒裂殖酵母的 rRNA 和核糖体蛋白合成产生不同的影响。
  • DOI:
    10.1007/bf00424424
  • 发表时间:
    1988
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Yamagishi,M;Nomura,M
  • 通讯作者:
    Nomura,M
Secondary structure of the autoregulatory mRNA binding site of ribosomal protein L1.
核糖体蛋白 L1 的自动调节 mRNA 结合位点的二级结构。
Mutational analysis of the L1 binding site of 23S rRNA in Escherichia coli.
大肠杆菌23S rRNA L1结合位点的突变分析。
  • DOI:
    10.1093/nar/16.22.10529
  • 发表时间:
    1988
  • 期刊:
  • 影响因子:
    14.9
  • 作者:
    Said,B;Cole,JR;Nomura,M
  • 通讯作者:
    Nomura,M
Mutational alterations of translational coupling in the L11 ribosomal protein operon of Escherichia coli.
大肠杆菌 L11 核糖体蛋白操纵子翻译耦合的突变改变。
  • DOI:
    10.1128/jb.169.8.3495-3507.1987
  • 发表时间:
    1987
  • 期刊:
  • 影响因子:
    3.2
  • 作者:
    Sor,F;Bolotin-Fukuhara,M;Nomura,M
  • 通讯作者:
    Nomura,M
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Masayasu Nomura其他文献

Masayasu Nomura的其他文献

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{{ truncateString('Masayasu Nomura', 18)}}的其他基金

DEFINING REGULATORS OF RNA POLYMERASE I FUNCTION IN S CEREVISIAE
定义酿酒酵母中 RNA 聚合酶 I 功能的调节因子
  • 批准号:
    7602218
  • 财政年份:
    2007
  • 资助金额:
    $ 32.38万
  • 项目类别:
DEFINING REGULATORS OF RNA POLYMERASE I FUNCTION IN S CEREVISIAE
定义酿酒酵母中 RNA 聚合酶 I 功能的调节因子
  • 批准号:
    7420695
  • 财政年份:
    2006
  • 资助金额:
    $ 32.38万
  • 项目类别:
REGULATORS OF SACCHAROMYCES RNA POLYMERASE I
酵母菌 RNA 聚合酶 I 的调节因子
  • 批准号:
    6979598
  • 财政年份:
    2004
  • 资助金额:
    $ 32.38万
  • 项目类别:
GENETICS AND BIOCHEMISTRY OF RIBOSOME SYNTHESIS
核糖体合成的遗传学和生物化学
  • 批准号:
    6385605
  • 财政年份:
    1985
  • 资助金额:
    $ 32.38万
  • 项目类别:
GENETICS AND BIOCHEMISTRY OF RIBOSOME SYNTHESIS
核糖体合成的遗传学和生物化学
  • 批准号:
    2178153
  • 财政年份:
    1985
  • 资助金额:
    $ 32.38万
  • 项目类别:
GENETICS AND BIOCHEMISTRY OF RIBOSOME BIOSYNTHESIS
核糖体生物合成的遗传学和生物化学
  • 批准号:
    3289439
  • 财政年份:
    1985
  • 资助金额:
    $ 32.38万
  • 项目类别:
GENETICS AND BIOCHEMISTRY OF RIBOSOME BIOSYNTHESIS
核糖体生物合成的遗传学和生物化学
  • 批准号:
    3289438
  • 财政年份:
    1985
  • 资助金额:
    $ 32.38万
  • 项目类别:
GENETICS AND BIOCHEMISTRY OF RIBOSOME BIOSYNTHESIS
核糖体生物合成的遗传学和生物化学
  • 批准号:
    3484829
  • 财政年份:
    1985
  • 资助金额:
    $ 32.38万
  • 项目类别:
GENETICS AND BIOCHEMISTRY OF RIBOSOME BIOSYNTHESIS
核糖体生物合成的遗传学和生物化学
  • 批准号:
    3484827
  • 财政年份:
    1985
  • 资助金额:
    $ 32.38万
  • 项目类别:
GENETICS AND BIOCHEMISTRY OF RIBOSOME SYNTHESIS
核糖体合成的遗传学和生物化学
  • 批准号:
    3484828
  • 财政年份:
    1985
  • 资助金额:
    $ 32.38万
  • 项目类别:

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