MECHANISTIC ANALYSIS OF AN RNA ENZYME IN VIVO

体内 RNA 酶的机理分析

基本信息

  • 批准号:
    6520371
  • 负责人:
  • 金额:
    $ 31.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-03-01 至 2005-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (adapted from applicant's abstract): The goal of the proposed research is to exploit the hairpin ribozyme and the power of mechanistic enzymology to develop a detailed, quantitative view of the kinetics and equilibria of RNA-mediated reactions in living cells. RNAs are critical components of the biological machinery responsible for maintenance and expression of genetic information, providing potential targets and reagents for therapeutic intervention. The dynamics and equilibria of RNA conformational transitions play key roles in transcription, translation and RNA processing reactions. Determining the functional significance of specific structures and conformational transitions in RNA-mediated biological processes is complicated by the participation of many components in complex pathways. On the other hand, mechanistic studies of RNA enzymes in vitro have produced detailed, quantitative descriptions of the kinetics and equilibria of individual steps of RNA-mediated reactions and the influence of small molecules, RNA binding proteins, and RNA transcription on RNA assembly pathways. The hairpin ribozyme provides an especially valuable model system for RNA structure-function studies in vivo because ribozyme variants can be designed so that intracellular cleavage activity monitors specific RNA conformational transitions along the reaction pathway. Mechanistic insights gleaned using this simple system to report on RNA structure and dynamics in specific biological contexts will help illuminate mechanisms of more complex RNA-mediated reactions and provide a rational framework for the development of RNA-based therapeutics. Specific goals include: establishing a kinetic and thermodynamic framework for mechanistic studies of RNA conformational transitions in vivo, determining whether RNA structures display different conformational equilibria and dynamics in nuclear and cytoplasmic compartments, determining how transcription and translation influence RNA assembly pathways in vivo, characterizing allosteric regulation of RNA structure and function by small molecule and protein effectors in vivo, and developing a system for ribozyme-mediated mRNA repair through sequential cleavage and ligation reactions. Mechanistic insights gleaned using the hairpin ribozyme to report on RNA structure and dynamics in specific biological contexts will help illuminate mechanisms of more complex RNA-mediated reactions and provide a rational framework for the development of RNA-based therapeutics.
描述(改编自申请人摘要):提议的目标

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Martha J. Fedor其他文献

The catalytic diversity of RNAs
RNA 的催化多样性
  • DOI:
    10.1038/nrm1647
  • 发表时间:
    2005-05-01
  • 期刊:
  • 影响因子:
    90.200
  • 作者:
    Martha J. Fedor;James R. Williamson
  • 通讯作者:
    James R. Williamson

Martha J. Fedor的其他文献

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{{ truncateString('Martha J. Fedor', 18)}}的其他基金

Catalytic Mechanisms of RNA Ezymes
RNA酶的催化机制
  • 批准号:
    8008948
  • 财政年份:
    2010
  • 资助金额:
    $ 31.11万
  • 项目类别:
Nucleic Acids Gordon Research Conference 2005
2005 年核酸戈登研究会议
  • 批准号:
    6932777
  • 财政年份:
    2005
  • 资助金额:
    $ 31.11万
  • 项目类别:
MECHANISTIC ANALYSIS OF AN RNA ENZYME IN VIVO
体内 RNA 酶的机理分析
  • 批准号:
    6636545
  • 财政年份:
    2001
  • 资助金额:
    $ 31.11万
  • 项目类别:
Mechanistic Analysis of Intracellular RNA Folding
细胞内RNA折叠的机制分析
  • 批准号:
    8098380
  • 财政年份:
    2001
  • 资助金额:
    $ 31.11万
  • 项目类别:
Mechanistic Analysis of Intracellular RNA Folding
细胞内RNA折叠的机制分析
  • 批准号:
    8654339
  • 财政年份:
    2001
  • 资助金额:
    $ 31.11万
  • 项目类别:
MECHANISTIC ANALYSIS OF AN RNA ENZYME IN VIVO
体内 RNA 酶的机理分析
  • 批准号:
    6711731
  • 财政年份:
    2001
  • 资助金额:
    $ 31.11万
  • 项目类别:
Mechanistic Analysis of an RNA Enzyme In Vivo
体内 RNA 酶的机理分析
  • 批准号:
    7253347
  • 财政年份:
    2001
  • 资助金额:
    $ 31.11万
  • 项目类别:
Mechanistic Analysis of an RNA Enzyme In Vivo
体内 RNA 酶的机理分析
  • 批准号:
    7145155
  • 财政年份:
    2001
  • 资助金额:
    $ 31.11万
  • 项目类别:
Mechanistic Analysis of Intracellular RNA Folding
细胞内RNA折叠的机制分析
  • 批准号:
    8462989
  • 财政年份:
    2001
  • 资助金额:
    $ 31.11万
  • 项目类别:
MECHANISTIC ANALYSIS OF AN RNA ENZYME IN VIVO
体内 RNA 酶的机理分析
  • 批准号:
    6228427
  • 财政年份:
    2001
  • 资助金额:
    $ 31.11万
  • 项目类别:

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