The role played by the RNAs and tRNAs in translation

RNA 和 tRNA 在翻译中发挥的作用

基本信息

  • 批准号:
    7151944
  • 负责人:
  • 金额:
    $ 25.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1999
  • 资助国家:
    美国
  • 起止时间:
    1999-05-01 至 2009-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Translation of the genetic information in the cell into functional proteins is an essential and highly conserved function. The ribosome, a two-subunit macromolecular complex, composed in bacteria of three large RNAs (rRNAs) and more than 50 proteins, is the catalyst and framework for the intricate and coordinated process of translation. Theoretical considerations, biochemical, genetic and now structural evidence indicate that the rRNAs play a central role in the processes of translation including aminoacyl tRNA loading, peptide bond formation, translocation of the mRNA:tRNA complex and peptide release. Our general goals are to define the molecular details of the translation process by focusing on the role played by the rRNAs in each of these basic steps. While structural information has provided us with candidates regions that may play direct roles in catalysis and movement, we are unable to define their specific role in the absence of biochemical dissection. Further, the dynamics of the translation cycle have been difficult to extract from the static views that we obtain from X-ray crystallography and cryoEM approaches. This proposal outlines a series of experiments focused on using pre-steady state kinetic analysis to define the contributions of specific rRNA elements to the different steps in translation. Site-directed mutagenesis will target critical regions and an in vivo tagging system will be used to allow for the isolation of variant ribosomes in vitro. Stopped-flow fluorescence will be used to monitor tRNA binding, release factor interactions and translocation while rapid quench approaches will be used to study the rates of GTP hydrolysis, peptide bond formation and peptide release. Chemical modification experiments and genetic screens are also proposed to assist in the identification of other regions of the rRNA that are critical in the dynamics of translation. Information obtained from such studies will help in defining the features of current antibiotics that make them effective and ultimately in the design of the new classes of therapeutic compounds.
描述(由申请人提供):将细胞中的遗传信息翻译成功能蛋白质是一项基本的和高度保守的功能。核糖体是细菌中由三个大RNA(RRNAs)和50多种蛋白质组成的两个亚单位的大分子复合体,是复杂而协调的翻译过程的催化剂和框架。理论考虑、生化、遗传和现在的结构证据表明,rRNAs在翻译过程中发挥核心作用,包括氨酰tRNA负载、肽键形成、mRNA:tRNA复合体的移位和肽的释放。我们的总体目标是通过关注rRNA在每个基本步骤中所起的作用来定义翻译过程的分子细节。虽然结构信息为我们提供了可能在催化和运动中发挥直接作用的候选区域,但在没有生化解剖的情况下,我们无法确定它们的具体作用。此外,从我们从X射线结晶学和低温电子显微镜方法获得的静态视图中很难提取翻译周期的动力学。该提案概述了一系列实验,重点是使用稳态前动力学分析来确定特定rRNA元件对翻译的不同步骤的贡献。定点突变将针对关键区域,体内标记系统将用于在体外分离变异核糖体。停流荧光将被用来监测tRNA的结合、释放因子的相互作用和易位,而快速猝灭方法将被用来研究GTP的水解率、肽键的形成和肽的释放。还建议进行化学修饰实验和遗传筛选,以帮助识别rRNA的其他在翻译动力学中至关重要的区域。从这类研究中获得的信息将有助于确定目前使其有效的抗生素的特征,并最终用于设计新类别的治疗性化合物。

项目成果

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RACHEL GREEN其他文献

RACHEL GREEN的其他文献

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{{ truncateString('RACHEL GREEN', 18)}}的其他基金

Biochemistry, Cellular and Molecular Biology Program: JHU BioGREAT (Biomedical Graduate REsiliency & Adaptability Training)
生物化学、细胞和分子生物学项目:JHU BioGREAT(生物医学研究生 REsiliency
  • 批准号:
    10810143
  • 财政年份:
    2022
  • 资助金额:
    $ 25.43万
  • 项目类别:
Biochemistry, Cellular and Molecular Biology Program
生物化学、细胞和分子生物学项目
  • 批准号:
    10650714
  • 财政年份:
    2022
  • 资助金额:
    $ 25.43万
  • 项目类别:
Biochemistry, Cellular and Molecular Biology Program
生物化学、细胞和分子生物学项目
  • 批准号:
    10332103
  • 财政年份:
    2022
  • 资助金额:
    $ 25.43万
  • 项目类别:
2013 Nucleic Acids Gordon Research Conference
2013年核酸戈登研究会议
  • 批准号:
    8516667
  • 财政年份:
    2013
  • 资助金额:
    $ 25.43万
  • 项目类别:
Kinetic Dissection of Eukaryotic Translation Initiation
真核翻译起始的动力学剖析
  • 批准号:
    8469510
  • 财政年份:
    2000
  • 资助金额:
    $ 25.43万
  • 项目类别:
DEFINING THE ROLE PLAYED BY 23S RRNA IN TRANSLATION
定义 23S RRNA 在翻译中所扮演的角色
  • 批准号:
    6182196
  • 财政年份:
    1999
  • 资助金额:
    $ 25.43万
  • 项目类别:
DEFINING THE ROLE PLAYED BY 23S RRNA IN TRANSLATION
定义 23S RRNA 在翻译中所扮演的角色
  • 批准号:
    2835607
  • 财政年份:
    1999
  • 资助金额:
    $ 25.43万
  • 项目类别:
The role played by the RNAs and tRNAs in translation
RNA 和 tRNA 在翻译中发挥的作用
  • 批准号:
    7529208
  • 财政年份:
    1999
  • 资助金额:
    $ 25.43万
  • 项目类别:
The role played by the RNAs and tRNAs in translation
RNA 和 tRNA 在翻译中发挥的作用
  • 批准号:
    7031934
  • 财政年份:
    1999
  • 资助金额:
    $ 25.43万
  • 项目类别:
The role played by the RNAs and tRNAs in translation
RNA 和 tRNA 在翻译中发挥的作用
  • 批准号:
    8010950
  • 财政年份:
    1999
  • 资助金额:
    $ 25.43万
  • 项目类别:
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