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
- 来源:
- 关键词:
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
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 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:
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