Mechanism and biology of widespread distal 3'UTR utilization in the CNS

CNS 中广泛使用远端 3UTR 的机制和生物学

基本信息

  • 批准号:
    8791352
  • 负责人:
  • 金额:
    $ 48.09万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-01-15 至 2018-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Mechanism and biology of widespread distal 3'UTR utilization in the CNS The 3' untranslated regions (3'UTRs) of messenger RNAs (mRNAs) are the predominant location of cis-regulatory sequences that mediate post-transcriptional gene regulation. 3'UTRs can impart profound positive or negative regulatory impact on gene function, via diverse RNA binding proteins (RBPs) and short RNAs termed microRNAs (miRNAs). In recent years, it has been appreciated that alternative polyadenylation (APA) can induce 3'UTR variation according to cell-state, tissue identity or environmental condition, providing a strategy for coordinate post-transcriptional regulation of hundreds of genes. However, the molecular mechanisms of APA are mostly unknown and only for a few genes have the consequences of disrupting APA been studied in intact animals. We recently described broad tissue-specific APA trends in Drosophila, including substantial 3'UTR lengthening in the central nervous system. This included hundreds of unannotated extensions, ranging into lengths unprecedented for experimentally- validated 3'UTRs of stable transcripts detected by Northern analysis. Our ongoing unpublished efforts reveal that these principles are broadly conserved in the mammalian brain. Altogether, the existence of these unexpectedly broad and long 3'UTR extensions has strong implications for gene regulation in the nervous system. In particular, we hypothesize that they mediate critical aspects of the unique post-transcriptional needs of neurons, imposed by their unusual cellular architecture. Our extensive preliminary data are the basis of diverse experimental strategies that we propose to elucidate the genomic breadth, the biological utility, and mechanistic underpinning to neural 3'UTR lengthening in Drosophila and mammalian systems. The proposed work exploits our established expertise with transcriptome analysis, miRNAs, post-transcriptional control, and neural development and function. We believe that the knowledge gained from our mechanistic and functional studies will have direct relevance for human disease. Dysfunction of the neuronal APA network may induce neurological conditions, while ectopic activation of the 3'UTR lengthening mechanism should severely distort gene regulatory networks outside of the brain. Our multi-faceted research program should illuminate these processes.
信使rna (mrna)的3‘非翻译区(3’ utrs)是介导转录后基因调控的顺式调控序列的主要位置。3' utr可以通过多种RNA结合蛋白(rbp)和被称为microRNAs (miRNAs)的短RNA,对基因功能产生深远的积极或消极的调节影响。近年来,人们认识到选择性聚腺苷化(APA)可以根据细胞状态、组织特性或环境条件诱导3'UTR变异,并提供了一种策略

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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Eric C Lai其他文献

Eric C Lai的其他文献

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{{ truncateString('Eric C Lai', 18)}}的其他基金

Essential roles for RNAi/hpRNAs to resolve intragenomic conflicts in the male germline
RNAi/hpRNA 在解决雄性种系基因组内冲突中的重要作用
  • 批准号:
    10617394
  • 财政年份:
    2022
  • 资助金额:
    $ 48.09万
  • 项目类别:
Essential roles for RNAi/hpRNAs to resolve intragenomic conflicts in the male germline
RNAi/hpRNA 在解决雄性种系基因组内冲突中的重要作用
  • 批准号:
    10467212
  • 财政年份:
    2022
  • 资助金额:
    $ 48.09万
  • 项目类别:
Mechanism and biology of widespread distal 3'UTR utilization in the CNS
CNS 中广泛使用远端 3UTR 的机制和生物学
  • 批准号:
    9208172
  • 财政年份:
    2014
  • 资助金额:
    $ 48.09万
  • 项目类别:
Mechanism and regulation of Hu family RNA binding proteins during neural alternative polyadenylation
Hu家族RNA结合蛋白在神经选择性多聚腺苷酸化过程中的机制和调控
  • 批准号:
    10328897
  • 财政年份:
    2014
  • 资助金额:
    $ 48.09万
  • 项目类别:
Mechanism and regulation of Hu family RNA binding proteins during neural alternative polyadenylation
Hu家族RNA结合蛋白在神经选择性多聚腺苷酸化过程中的机制和调控
  • 批准号:
    10543867
  • 财政年份:
    2014
  • 资助金额:
    $ 48.09万
  • 项目类别:
Mechanism and biology of widespread distal 3'UTR utilization in the CNS
CNS 中广泛使用远端 3UTR 的机制和生物学
  • 批准号:
    8698063
  • 财政年份:
    2014
  • 资助金额:
    $ 48.09万
  • 项目类别:
BEN factors are conserved CSL co-repressors in Notch-mediated neural development
BEN 因子是 Notch 介导的神经发育中保守的 CSL 共抑制因子
  • 批准号:
    8325028
  • 财政年份:
    2011
  • 资助金额:
    $ 48.09万
  • 项目类别:
BEN factors are conserved CSL co-repressors in Notch-mediated neural development
BEN 因子是 Notch 介导的神经发育中保守的 CSL 共抑制因子
  • 批准号:
    8730239
  • 财政年份:
    2011
  • 资助金额:
    $ 48.09万
  • 项目类别:
BEN factors are conserved CSL co-repressors in Notch-mediated neural development
BEN 因子是 Notch 介导的神经发育中保守的 CSL 共抑制因子
  • 批准号:
    8535849
  • 财政年份:
    2011
  • 资助金额:
    $ 48.09万
  • 项目类别:
BEN factors are conserved CSL co-repressors in Notch-mediated neural development
BEN 因子是 Notch 介导的神经发育中保守的 CSL 共抑制因子
  • 批准号:
    8239327
  • 财政年份:
    2011
  • 资助金额:
    $ 48.09万
  • 项目类别:

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