The Role of Aminoacyl-tRNA Synthesis In Translational Quality Control

氨酰基-tRNA 合成在翻译质量控制中的作用

基本信息

项目摘要

The correct functioning of living systems requires maintaining a certain level of fidelity in all processes dealing with the transfer of information. Translation is the process by which genetic information is transferred from a nucleic acid sequence into the amino acid sequence of a protein. The fidelity of translation is determined at two major points: the accuracy of aminoacyl-tRNA selection by the ribosomes and synthesis of cognate amino acid/tRNA pairs by aminoacyl-tRNA synthetases (aaRS) in the course of the aminoacylation reaction. The aaRSs define the genetic code by pairing tRNAs with the corresponding amino acids. Accurate aminoacyl-tRNA synthesis often involves an additional editing activity intrinsic to many aaRSs. The editing activity significantly decreases the level of mistakes in aminoacyl-tRNA synthesis in vitro and in vivo, although quantitative analysis of its contribution to the overall fidelity of translation has not been performed. The overall aim of this project is to develop experimental systems to quantitatively measure the frequency of aaRS-dependent misincorporation for several amino acids and evaluate the contribution of aaRS editing to overall translational fidelity. The intellectual merits of this research are in achieving significant progress in understanding fundamental biological problems, namely fidelity control in general and the editing mechanisms employed during translation in particular. The broader impacts resulting from the project will be to provide integrated laboratory research and training programs for both undergraduate and graduate students and to establish a new collaborative network.
生命系统的正确运作需要在处理信息传递的所有过程中保持一定程度的保真度。翻译是遗传信息从核酸序列转移到蛋白质氨基酸序列的过程。翻译的保真度主要取决于两点:核糖体选择氨酰-tRNA的准确性和氨酰化反应过程中氨酰-tRNA合成酶(阿尔斯)合成同源氨基酸/tRNA对的准确性。aaRS通过将tRNA与相应的氨基酸配对来定义遗传密码。准确的氨酰-tRNA合成通常涉及许多aaRS固有的额外编辑活性。编辑活动显着降低水平的错误在氨酰-tRNA合成在体外和体内,虽然其贡献的整体保真度的翻译尚未进行定量分析。该项目的总体目标是开发实验系统,以定量测量几种氨基酸的aaRS依赖性错误掺入的频率,并评估阿尔斯编辑对整体翻译保真度的贡献。这项研究的智力价值在于在理解基本生物学问题方面取得了重大进展,即一般的保真度控制和特别是翻译过程中采用的编辑机制。该项目产生的更广泛的影响将是为本科生和研究生提供综合实验室研究和培训计划,并建立一个新的合作网络。

项目成果

期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)

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Michael Ibba其他文献

Genetic analysis of functional connectivity between substrate recognition domains ofEscherichia coli glutaminyl-tRNA synthetase
大肠杆菌谷氨酰胺酰-tRNA合成酶底物识别域之间功能连接的遗传分析
  • DOI:
  • 发表时间:
    1996
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Makoto Kitabatake;Hachiro Inokuchi;Michael Ibba;Kwang;Dieter Söll
  • 通讯作者:
    Dieter Söll
AARS Online: a collaborative database on the structure, function, and evolution of the aminoacyl-tRNA synthetases
AARS Online:关于氨酰基-tRNA 合成酶的结构、功能和进化的协作数据库
  • DOI:
    10.1101/2024.05.15.594223
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    J. Douglas;Haissi Cui;John J. Perona;O. Vargas;H. Tyynismaa;Claudia Alvarez Carreño;Jiqiang Ling;Lluís Ribas;Xiang;Michael Ibba;Hubert D. Becker;Frédéric Fischer;Marie Sissler;Charles W. Carter;Peter R. Wills
  • 通讯作者:
    Peter R. Wills
Stable continuous constitutive expression of a heterologous protein in Saccharomyces cerevisiae without selection pressure
  • DOI:
    10.1007/bf00205045
  • 发表时间:
    1993-07-01
  • 期刊:
  • 影响因子:
    4.300
  • 作者:
    Michael Ibba;Jochen Kuhla;Alan Smith;Martin Küenzi
  • 通讯作者:
    Martin Küenzi
Sticky end in protein synthesis
蛋白质合成中的粘性末端
  • DOI:
    10.1038/nature05002
  • 发表时间:
    2006-08-13
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Hervé Roy;Michael Ibba
  • 通讯作者:
    Michael Ibba
What is microbial dormancy?
什么是微生物休眠?
  • DOI:
    10.1016/j.tim.2023.08.006
  • 发表时间:
    2024-02-01
  • 期刊:
  • 影响因子:
    14.900
  • 作者:
    Mark D. McDonald;Carlos Owusu-Ansah;Jared B. Ellenbogen;Zachary D. Malone;Michael P. Ricketts;Steve E. Frolking;Jessica Gilman Ernakovich;Michael Ibba;Sarah C. Bagby;J.L. Weissman
  • 通讯作者:
    J.L. Weissman

Michael Ibba的其他文献

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{{ truncateString('Michael Ibba', 18)}}的其他基金

COLLABORATIVE RESEARCH: The role of quality control in microbial translation
合作研究:质量控制在微生物翻译中的作用
  • 批准号:
    2101998
  • 财政年份:
    2020
  • 资助金额:
    $ 54.3万
  • 项目类别:
    Standard Grant
COLLABORATIVE RESEARCH: The role of quality control in microbial translation
合作研究:质量控制在微生物翻译中的作用
  • 批准号:
    1715840
  • 财政年份:
    2017
  • 资助金额:
    $ 54.3万
  • 项目类别:
    Standard Grant
COLLABORATIVE RESEARCH: The role of quality control in microbial translation
合作研究:质量控制在微生物翻译中的作用
  • 批准号:
    1412611
  • 财政年份:
    2014
  • 资助金额:
    $ 54.3万
  • 项目类别:
    Continuing Grant
COLLABORATIVE RESEARCH: The Role of Quality Control in Microbial Translation
合作研究:质量控制在微生物翻译中的作用
  • 批准号:
    1052344
  • 财政年份:
    2011
  • 资助金额:
    $ 54.3万
  • 项目类别:
    Continuing Grant
Collaborative Research: The Role of Quality Control in Microbial Translation
合作研究:质量控制在微生物翻译中的作用
  • 批准号:
    0744791
  • 财政年份:
    2008
  • 资助金额:
    $ 54.3万
  • 项目类别:
    Continuing Grant
Collaborative Research: The Role of Quality Control in Microbial Translation
合作研究:质量控制在微生物翻译中的作用
  • 批准号:
    0936068
  • 财政年份:
    2008
  • 资助金额:
    $ 54.3万
  • 项目类别:
    Continuing Grant

相似国自然基金

基于Aminoacyl-tRNA合成酶途径探索胆道闭锁KPE术后转归早期生物标志物及构建风险预警模型研究
  • 批准号:
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    省市级项目

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Structural design of aminoacyl-tRNA synthetase based on predicted structures: Application to production of highly functional proteins
基于预测结构的氨酰-tRNA合成酶的结构设计:在高功能蛋白质生产中的应用
  • 批准号:
    23K19288
  • 财政年份:
    2023
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    $ 54.3万
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    Grant-in-Aid for Research Activity Start-up
Biological significance of aminoacyl-tRNA synthetases in hematopoietic malignancies
氨酰-tRNA合成酶在造血系统恶性肿瘤中的生物学意义
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    23K19536
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    2023
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Meeting on Aminoacyl-tRNA Synthetases 2023
2023 年氨酰基-tRNA 合成酶会议
  • 批准号:
    468221
  • 财政年份:
    2022
  • 资助金额:
    $ 54.3万
  • 项目类别:
    Miscellaneous Programs
Discovering the roles of aminoacyl tRNA synthetases through mutant histidine aminoacyl tRNA synthetase function
通过突变组氨酸氨酰 tRNA 合成酶功能发现氨酰 tRNA 合成酶的作用
  • 批准号:
    486061
  • 财政年份:
    2022
  • 资助金额:
    $ 54.3万
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An aminoacyl tRNA synthetase is a nitrogen sensor that activates TOR in plants
氨酰 tRNA 合成酶是一种氮传感器,可激活植物中的 TOR
  • 批准号:
    10484171
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    2021
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Defining the Role of Aminoacyl-tRNA Synthetases in Human Health and Disease
定义氨酰基-tRNA 合成酶在人类健康和疾病中的作用
  • 批准号:
    10654600
  • 财政年份:
    2020
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Analysis of amino acid specificity of aminoacyl-tRNA synthetase before last universal common ancestor
最后通用共同祖先之前氨酰-tRNA合成酶的氨基酸特异性分析
  • 批准号:
    20K14598
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Resurrection of ancestral aminoacyl tRNA synthetase and stepwise construction of ancestral translation system
祖传氨酰tRNA合成酶的复活与祖传翻译系统的逐步构建
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    20H02018
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    $ 54.3万
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寻找氨酰-tRNA合成酶的新生理功能及其调控机制
  • 批准号:
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定义氨酰基-tRNA 合成酶在人类健康和疾病中的作用
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