lncRNAs as Organizers of and Bridges Between Proteins and DNA

lncRNA 作为蛋白质和 DNA 的组织者和桥梁

基本信息

  • 批准号:
    9158537
  • 负责人:
  • 金额:
    $ 37.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-22 至 2020-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary One of the unexpected developments in the last decade emerged from large scale sequencing efforts - the discovery of widespread genome-wide transcription. While the human genome project revealed an unexpectedly small fraction of the genome dedicated to protein-coding genes, the ENCODE and related projects revealed that at least 70% of the genome is actively transcribed. This led to the discovery of a new class of RNAs known as long non-coding RNAs or lncRNAs. Rapidly accumulating evidence strongly suggests that these lncRNAs have important autonomous activities as RNAs. The emerging functions are predominantly in development, differentiation and pluripotency, processes with critical links to human health. Thus, establishing an understanding of the mechanism of action of lncRNAs is a high priority frontier in biology. Towards the long term-goal of producing a molecular understanding of lncRNA function, we are using a set of biochemical and structural approaches to elucidate how lncRNAs organize aspects of the nucleus to regulate and coordinate chromatin expression. In the first Aim of our proposed research program, the molecular basis of the interaction between hnRNP U and the Xist and Firre RNAs will be investigated. These lncRNAs are essential for X-chromosome inactivation (Xist) and adipogenesis (Firre), using mechanisms requiring their direct interaction with hnRNP U that localizes the lncRNA to the correct chromosome or loci. Selective binding of the RNA-binding RGG domain of hnRNP U will be explored using a combination of "bottom-up" and "top-down" biochemical approaches and structural approaches to understand the molecular details of protein-RNA recognition, focusing on the critical but poorly understood RGG domain. The results of these studies will illuminate a number of RNA-protein interactions mediated by RGG domains that are central to human RNA metabolism. The second Aim focuses on the decoy/guide model for lncRNA function by investigating the interactions of two key transcription factors, glucocorticoid receptor (GR) and Sox2, with the lncRNAs that are proposed to modulate the specificity and regulatory activity of these proteins. According to this model, pervasive transcription at promoters and enhancers can either titrate away a transcription factor from its dsDNA-binding site or, conversely, help to recruit and localize a transcription factor to a target. To reveal the sequences and/or structures of lncRNAs that these dsDNA-binding proteins can recognize, an in vitro selection based approach will be used and the results correlated with transcriptomic studies. In parallel, traditional biochemical and structural approaches will be used to understand the molecular details of these protein-RNA interactions with known lncRNA targets. These studies will yield direct insights into how key transcription factors that have classically been regarded as solely dsDNA-binding factors also interact with RNA as a critical part of their gene regulatory mechanism.
项目总结

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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Robert T Batey其他文献

Robert T Batey的其他文献

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{{ truncateString('Robert T Batey', 18)}}的其他基金

Riboglow: a robust multi-color riboswitch-based platform for imaging RNA in living cells
Riboglow:基于多色核糖开关的强大平台,用于活细胞中 RNA 成像
  • 批准号:
    9904726
  • 财政年份:
    2019
  • 资助金额:
    $ 37.17万
  • 项目类别:
Riboglow: a robust multi-color riboswitch-based platform for imaging RNA in living cells
Riboglow:基于多色核糖开关的强大平台,用于活细胞中 RNA 成像
  • 批准号:
    9764689
  • 财政年份:
    2019
  • 资助金额:
    $ 37.17万
  • 项目类别:
Riboglow: a robust multi-color riboswitch-based platform for imaging RNA in living cells
Riboglow:基于多色核糖开关的强大平台,用于活细胞中 RNA 成像
  • 批准号:
    10374881
  • 财政年份:
    2019
  • 资助金额:
    $ 37.17万
  • 项目类别:
lncRNAs as Organizers of and Bridges Between Proteins and DNA
lncRNA 作为蛋白质和 DNA 的组织者和桥梁
  • 批准号:
    9356528
  • 财政年份:
    2016
  • 资助金额:
    $ 37.17万
  • 项目类别:
Purchase of an Isothermal Titration Calorimeter
购买等温滴定量热计
  • 批准号:
    7792160
  • 财政年份:
    2010
  • 资助金额:
    $ 37.17万
  • 项目类别:
Structure and Mechanism of SAM-responsive Riboswitches
SAM响应核糖开关的结构和机制
  • 批准号:
    7434273
  • 财政年份:
    2008
  • 资助金额:
    $ 37.17万
  • 项目类别:
Structure and Mechanism of SAM-responsive Riboswitches
SAM响应核糖开关的结构和机制
  • 批准号:
    8036043
  • 财政年份:
    2008
  • 资助金额:
    $ 37.17万
  • 项目类别:
Structure and Mechanism of SAM-responsive Riboswitches
SAM响应核糖开关的结构和机制
  • 批准号:
    8369542
  • 财政年份:
    2008
  • 资助金额:
    $ 37.17万
  • 项目类别:
Structure and Mechanism of SAM-responsive Riboswitches
SAM响应核糖开关的结构和机制
  • 批准号:
    8516526
  • 财政年份:
    2008
  • 资助金额:
    $ 37.17万
  • 项目类别:
Structure and Mechanism of SAM-responsive Riboswitches
SAM响应核糖开关的结构和机制
  • 批准号:
    7616428
  • 财政年份:
    2008
  • 资助金额:
    $ 37.17万
  • 项目类别:

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顺式作用 NF1 样结合位点对细胞特异性基因表达的调节功能及其 DNA 结合蛋白的表征
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