Administrative Supplement: Mechanisms of Spliceosome Assembly and Regulation

行政补充:剪接体组装与调控机制

基本信息

  • 批准号:
    10378361
  • 负责人:
  • 金额:
    $ 16.03万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-05-01 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT RNA splicing is a key feature of human gene expression and a major contributor to expansion of genetic information by alternative splicing. Splicing is carried out by a large and dynamic cellular machine called the spliceosome. Spliceosomes are composed of small nuclear ribonucleoproteins (snRNPs) that assemble on precursor transcripts (pre-mRNAs) to remove introns and splice together exons. This process must occur precisely in order to preserve the genetic information carried in the mRNA. Critical for splicing is the correct identification of the sites of RNA bond cleavage and formation [the 5' and 3' splice sites (SS) and the branch site (BS)]. A number of different ATPases contribute to the fidelity of SS and BS recognition as well as carry out extensive compositional and conformational remodeling of the spliceosome. Recently, biochemical studies of splicing have been transformed by determination of dozens of different structures of yeast and human spliceosomes by cryo-EM. Despite this structural revolution, much remains unknown about central features of the splicing reaction. The goal of my laboratory’s research is to elucidate mechanisms of spliceosome assembly and regulation in biochemical depth using a variety of techniques. We often use single molecule fluorescence microscopy to deconvolute the complex and heterogeneous reaction pathways employed by the splicing machinery. In recent work, we have studied mechanisms of 5'SS and BS recognition, assembly and dynamics of the U6 snRNP, and developed methods for fluorescently-labeling, purifying, and inhibiting RNAs and RNPs. Our vision for the next five years is to merge the insights obtained from structures of spliceosomes with single molecule, biochemical, computational, and genetic experiments to address outstanding gaps in our knowledge of splicing. These gaps include fundamental principles of RNP folding and assembly, the mechanisms of regulated splicing, and the scarcity of specific and effective chemical inhibitors of the spliceosome. As part of this vision, we will answer the following questions using multi-disciplinary approaches: 1) How do RNA and protein co-fold to assemble the U6 snRNP? 2) How is the spliceosome remodeled during creation of its active site? 3) How do regulatory proteins promote splicing at weak 5'SS? 4) How can we block ATPase-dependent transitions during splicing with small molecule inhibitors? 5) How do we quantitatively analyze, compare, and integrate cryo-EM structures of spliceosomes?
项目总结/文摘

项目成果

期刊论文数量(0)
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Aaron Andrew Hoskins其他文献

Aaron Andrew Hoskins的其他文献

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{{ truncateString('Aaron Andrew Hoskins', 18)}}的其他基金

Administrative Supplement: Mechanisms of Spliceosome Assembly and Regulation
行政补充:剪接体组装与调控机制
  • 批准号:
    10169637
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
Mechanisms of Spliceosome Assembly and Regulation
剪接体组装和调控机制
  • 批准号:
    10608952
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
Mechanisms of Spliceosome Assembly and Regulation
剪接体组装和调控机制
  • 批准号:
    10393514
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
Administrative Supplement: Mechanisms of Spliceosome Assembly and Regulation
行政补充:剪接体组装与调控机制
  • 批准号:
    10807767
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
Administrative Supplement: Mechanisms of Spliceosome Assembly and Regulation
行政补充:剪接体组装与调控机制
  • 批准号:
    10797871
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
Mechanisms of Spliceosome Assembly and Splice Site Recognition
剪接体组装和剪接位点识别的机制
  • 批准号:
    8996582
  • 财政年份:
    2015
  • 资助金额:
    $ 16.03万
  • 项目类别:
Mechanisms of Spliceosome Assembly and Splice Site Selection
剪接体组装和剪接位点选择的机制
  • 批准号:
    8308082
  • 财政年份:
    2008
  • 资助金额:
    $ 16.03万
  • 项目类别:
Mechanisms of Spliceosome Assembly and Splice Site Selection
剪接体组装和剪接位点选择的机制
  • 批准号:
    8535781
  • 财政年份:
    2008
  • 资助金额:
    $ 16.03万
  • 项目类别:
Mechanisms of Spliceosome Assembly and Splice Site Selection
剪接体组装和剪接位点选择的机制
  • 批准号:
    8325655
  • 财政年份:
    2008
  • 资助金额:
    $ 16.03万
  • 项目类别:
Single Molecule Analysis of Spliceosome Catalysis and Fidelity
剪接体催化和保真度的单分子分析
  • 批准号:
    7570401
  • 财政年份:
    2008
  • 资助金额:
    $ 16.03万
  • 项目类别:

相似海外基金

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健康和疾病中剪接位点选择的机制
  • 批准号:
    10797554
  • 财政年份:
    2023
  • 资助金额:
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  • 项目类别:
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  • 批准号:
    10460136
  • 财政年份:
    2021
  • 资助金额:
    $ 16.03万
  • 项目类别:
Quantitative and Predictive Analysis of 5' Splice Site Recognition by U1 snRNP using Massively Parallel Arrays
使用大规模并行阵列对 U1 snRNP 5 剪接位点识别进行定量和预测分析
  • 批准号:
    10311645
  • 财政年份:
    2021
  • 资助金额:
    $ 16.03万
  • 项目类别:
Uncovering Mechanisms of 5' Splice Site Fidelity
揭示 5 剪接位点保真度的机制
  • 批准号:
    10532793
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
How do RNA-binding proteins control splice site selection?
RNA 结合蛋白如何控制剪接位点选择?
  • 批准号:
    BB/T000627/1
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
    Research Grant
Mechanism of Splice Site Recognition by the U2AF/SF1 Protein Complex
U2AF/SF1 蛋白复合物的剪接位点识别机制
  • 批准号:
    553974-2020
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Uncovering Mechanisms of 5' Splice Site Fidelity
揭示 5 剪接位点保真度的机制
  • 批准号:
    10316181
  • 财政年份:
    2020
  • 资助金额:
    $ 16.03万
  • 项目类别:
Mechanisms of Splice Site Selection in Health and Disease
健康和疾病中剪接位点选择的机制
  • 批准号:
    10769989
  • 财政年份:
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    $ 16.03万
  • 项目类别:
Mechanisms of Splice Site Selection in Health and Disease
健康和疾病中剪接位点选择的机制
  • 批准号:
    10808389
  • 财政年份:
    2019
  • 资助金额:
    $ 16.03万
  • 项目类别:
Mechanisms of Splice Site Selection in Health and Disease
健康和疾病中剪接位点选择的机制
  • 批准号:
    10585911
  • 财政年份:
    2019
  • 资助金额:
    $ 16.03万
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