Nonsense-mediated mRNA decay: Pioneer round of translation

无义介导的 mRNA 衰变:首轮翻译

基本信息

  • 批准号:
    7908048
  • 负责人:
  • 金额:
    $ 19.27万
  • 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:
    2009-09-18 至 2011-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): We aim to continue our studies of the pioneer translation initiation complex and the pioneer round of translation. Nonsense-mediated mRNA decay (NMD) is an important quality control mechanism that eliminates transcripts having the potential to generate truncated proteins that could be deleterious to cells. We have found that NMD in mammalian cells generally occurs when translation terminates more than -50- 55 nts upstream of a splicing-generated exon-exon junction during a pioneer round of translation. By definition, this round of translation utilizes mRNA that is bound by the cap binding protein heterodimer CBP80/20. The role of the exon-exon junction in NMD reflects the post-splicing deposition of an exon junction complex (EJC) of proteins that include the Upf NMD factors. We have found that EJCs typify spliced CBP80/20-bound mRNA but not its remodeled product, elF4E-bound mRNA. To date, we have shown that the pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady- state, i.e., elF4E-bound, translation initiation complex. We have identified degradative activities involved in NMD. We also began to unravel why some mRNAs are subject to nucleus-associated NMD whereas other mRNAs are subject to cytoplasmic NMD. In Aim 1, we will study further the structure of the pioneer translation initiation complex before and during translation, and we will characterize the interacting domains of CBP80-Upf 1, CBP80-SMG1, CBP80-elF4GI, Upf 1 -eRF1 and Upf 1 -eRF3 that we have shown exist. In Aim 2, we will determine why some mRNAs are targeted for nucleus-associated NMD and other mRNAs are targeted for cytoplasmic NMD and, in collaboration with Rob Singer's lab, we will localize the cellular site of nucleus-associated NMD using fluorescent in situ hybridization of single RNA molecules. In Aim 3, we will solidify data obtained in collaboration with Ben Blencowe's lab indicating that there are functional differences among different EJCs or if any EJC that resides sufficiently downstream of a nonsense codon can trigger NMD. These differences will be exploited to determine if NMD is triggered by only the 3'-most EJC or if any EJC that resides more than 50-55 nucleotides downstream of a nonsense codon can trigger NMD. We expect that renewed support of this grant will allow us to continue to make major advances in understanding the mechanism of NMD in mammalian cells.
描述(由申请人提供):我们的目标是继续我们的研究先驱翻译启动复杂和翻译的先驱轮。无义介导的mRNA衰变(NMD)是一种重要的质量控制机制,其消除具有产生可能对细胞有害的截短蛋白质的潜力的转录物。我们已经发现,哺乳动物细胞中的NMD通常发生在翻译的先锋轮期间,当翻译终止于剪接产生的外显子-外显子连接点上游约50 - 55 nt时。根据定义,这一轮翻译利用由帽结合蛋白异二聚体CBP 80/20结合的mRNA。外显子-外显子连接在NMD中的作用反映了包括Upf NMD因子的蛋白质的外显子连接复合物(EJC)的剪接后沉积。我们已经发现EJC代表剪接的CBP 80/20结合的mRNA,但不是其重塑产物eIF 4 E结合的mRNA。到目前为止,我们已经表明,先锋翻译起始复合物在功能上不同于稳态,但在结构上与稳态重叠,即,eIF 4 E结合的翻译起始复合物。我们已经查明了国家导弹防御系统所涉及的一些破坏性活动。我们也开始解开为什么一些mRNA受到核相关的NMD,而其他mRNA受到细胞质NMD。目的一:进一步研究翻译前和翻译过程中先驱翻译起始复合物的结构,并对我们已经发现的CBP 80-Upf 1、CBP 80-SMG 1、CBP 80-eIF 4GI、Upf 1 -eRF 1和Upf 1 -eRF 3的相互作用结构域进行表征。在目标2中,我们将确定为什么一些mRNA针对核相关NMD,而其他mRNA针对细胞质NMD,并且与Rob Singer的实验室合作,我们将使用单个RNA分子的荧光原位杂交定位核相关NMD的细胞位点。在目标3中,我们将巩固与Ben Blencowe实验室合作获得的数据,这些数据表明不同EJC之间存在功能差异,或者位于无义密码子下游的任何EJC是否可以触发NMD。将利用这些差异来确定NMD是否仅由最3 '端的EJC触发,或者位于无义密码子下游超过50-55个核苷酸的任何EJC是否可以触发NMD。我们希望,对这笔赠款的重新支持将使我们能够继续在了解哺乳动物细胞中的NMD机制方面取得重大进展。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Lynne E Maquat其他文献

The power of point mutations
点突变的力量
  • DOI:
    10.1038/83759
  • 发表时间:
    2001-01-01
  • 期刊:
  • 影响因子:
    29.000
  • 作者:
    Lynne E Maquat
  • 通讯作者:
    Lynne E Maquat

Lynne E Maquat的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Lynne E Maquat', 18)}}的其他基金

Nonsense-mediated mRNA decay and beyond
无义介导的 mRNA 衰减及其他
  • 批准号:
    10622727
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
PHASING AND SOLVING THE CRYSTAL STRUCTURE OF A PORTION OF A STAU PROTEIN
定相并解析 STAU 蛋白部分的晶体结构
  • 批准号:
    8363563
  • 财政年份:
    2011
  • 资助金额:
    $ 19.27万
  • 项目类别:
2010 Post-Transcriptional Gene Regulation Biology of Gordon Research Conference
2010戈登研究会议转录后基因调控生物学
  • 批准号:
    7903519
  • 财政年份:
    2010
  • 资助金额:
    $ 19.27万
  • 项目类别:
Faculty Recruitment for the University of Rochester Center for RNA Biology Core
罗切斯特大学RNA生物学核心中心教师招聘
  • 批准号:
    7861230
  • 财政年份:
    2009
  • 资助金额:
    $ 19.27万
  • 项目类别:
Faculty Recruitment for the University of Rochester Center for RNA Biology Core
罗切斯特大学RNA生物学核心中心教师招聘
  • 批准号:
    7943922
  • 财政年份:
    2009
  • 资助金额:
    $ 19.27万
  • 项目类别:
Training in Cellular, Biochemical and Molecular Sciences
细胞、生化和分子科学培训
  • 批准号:
    8501513
  • 财政年份:
    2005
  • 资助金额:
    $ 19.27万
  • 项目类别:
Training in Cellular, Biochemical and Molecular Sciences
细胞、生化和分子科学培训
  • 批准号:
    8290493
  • 财政年份:
    2005
  • 资助金额:
    $ 19.27万
  • 项目类别:
Training in Cellular, Biochemical and Molecular Sciences
细胞、生化和分子科学培训
  • 批准号:
    7642274
  • 财政年份:
    2005
  • 资助金额:
    $ 19.27万
  • 项目类别:
Training in Cellular, Biochemical and Molecular Sciences
细胞、生化和分子科学培训
  • 批准号:
    7849807
  • 财政年份:
    2005
  • 资助金额:
    $ 19.27万
  • 项目类别:
Training in Cellular, Biochemical and Molecular Sciences
细胞、生化和分子科学培训
  • 批准号:
    7087861
  • 财政年份:
    2005
  • 资助金额:
    $ 19.27万
  • 项目类别:

相似海外基金

Collaborative Research: Tools 4 Cells: Developing Next Generation Methods for Studying Cytoskeletal Factors in the Cell Nucleus
合作研究:工具 4 细胞:开发研究细胞核中细胞骨架因子的下一代方法
  • 批准号:
    2306188
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Standard Grant
Evasion of antiviral responses in the host cell nucleus
逃避宿主细胞核中的抗病毒反应
  • 批准号:
    BB/X014126/1
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Research Grant
Collaborative Research: Tools 4 Cells: Developing Next Generation Methods for Studying Cytoskeletal Factors in the Cell Nucleus
合作研究:工具 4 细胞:开发研究细胞核中细胞骨架因子的下一代方法
  • 批准号:
    2306187
  • 财政年份:
    2023
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Standard Grant
Direct Manipulation in Cell Nucleus
细胞核的直接操作
  • 批准号:
    22H01441
  • 财政年份:
    2022
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of pH-sensitive size reducible nanoparticles for cell nucleus target delivery in multidrug-resistant breast cancer
开发用于多重耐药乳腺癌细胞核靶向递送的 pH 敏感尺寸可缩减纳米颗粒
  • 批准号:
    22K12822
  • 财政年份:
    2022
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Dissecting the sensory hair cell nucleus: Development of a novel method for investigating chromatin interactions (Tn5-Capture) in small cell numbers
解剖感觉毛细胞核:开发一种研究小细胞中染色质相互作用(Tn5-Capture)的新方法
  • 批准号:
    10571130
  • 财政年份:
    2022
  • 资助金额:
    $ 19.27万
  • 项目类别:
Molecular Analysis of Nuclear Bodies and RNP Trafficking Pathways in the Cell Nucleus
细胞核中核体和 RNP 运输途径的分子分析
  • 批准号:
    BB/V010948/1
  • 财政年份:
    2021
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Research Grant
Exploration of the modification of genomic higher-order structures in the cell nucleus by aggregation of chemically synthesized short nucleic acids
通过化学合成的短核酸聚集修饰细胞核内基因组高阶结构的探索
  • 批准号:
    21K19040
  • 财政年份:
    2021
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
3D analysis of chromatin structure in cell nucleus with electron microscopy and mathematical modeling
利用电子显微镜和数学建模对细胞核染色质结构进行 3D 分析
  • 批准号:
    21K18234
  • 财政年份:
    2021
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Pioneering)
Single particle dynamics of the NF-kB foci in the living cell nucleus
活细胞核中 NF-kB 焦点的单粒子动力学
  • 批准号:
    19K22404
  • 财政年份:
    2019
  • 资助金额:
    $ 19.27万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了