Regulation of Gene Expression by Dietary Fat

膳食脂肪对基因表达的调节

基本信息

  • 批准号:
    7624074
  • 负责人:
  • 金额:
    $ 27.33万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1993
  • 资助国家:
    美国
  • 起止时间:
    1993-08-01 至 2009-03-31
  • 项目状态:
    已结题

项目摘要

The amount and type of fat in the diet has been the subject of public health recommendations to prevent obesity, diabetes and atherosclerosis. A considerable body of literature has developed that suggests that eating the majority of calories as fat results in the development of insulin resistance and type II diabetes mellitus. Much less is known about how non-pathological fluctuations in dietary fat intake alter intracellular metabolism and how these signaling actions affect events in the nucleus. The glucose-6- phosphate dehydrogenase enzyme provides a unique model to study these nuclear events. First, its role as a lipogenic enzyme makes it important in the etiology of dyslipidemias. Second, it participates in the generation of a putative carbohydrate signaling molecule involved in the transcriptional regulation of both glycolytic and lipogenic genes. Finally, it is reglated at a unique posttranscriptional step permitting the exploration of new regulatory mechanisms beyond transcriptional regulation. We have demonstrated that polyunsaturated fatty acids decrease the rate of splicing of the G6PD pre-mRNA, while transcriptional activity of the gene is not regulated. The overall goal of this project is to understand the molecular mechanism for this regulated splicing. The objective of this application is to define the splicing regulatory proteins involved in this regulation of G6PD splicing and how polyunsaturated fats inhibit their activity. The central hypothesis of the application is that the splicing regulatory region of G6PD exon 12 contains juxtaposed splicing silencing and enhancing elements. The binding of hnRNP K and/or L to the silencer exclude the binding of splicing activators proteins to the enhancer. Polyunsaturated fatty acids regulate the activity of the splicing regulatory proteins by posttranslational modification and/or nuclear abundance. Despite the ubiquitous need for regulated splicing, little is known about the intracellular signals regulating this process. Our experiments are the first to describe inhibition of splicing as a mechanism for inhibition of gene expression by polyunsaturated fat. Thus, the experiments in the current proposal will provide new data on regulation of splicing pre se and define a new pathway by which nutrients regulate gene expression.
饮食中脂肪的数量和类型一直是公众健康的主题 建议预防肥胖、糖尿病和动脉粥样硬化。一个相当大的身体 大量的文献表明,摄入的大部分卡路里都是脂肪, 胰岛素抵抗和II型糖尿病的发展。之甚少 已知膳食脂肪摄入的非病理性波动如何改变细胞内 代谢以及这些信号作用如何影响细胞核中的事件。葡萄糖-6- 磷酸脱氢酶为研究这些核事件提供了一个独特的模型。 首先,其作为脂肪生成酶的作用使其在血脂异常的病因学中很重要。 第二,它参与了一个假定的碳水化合物信号分子的产生 参与糖酵解和脂肪生成基因的转录调控。最后, 它在一个独特的转录后步骤重新定位,允许探索新的 转录调控以外的调控机制。我们已经证明 多不饱和脂肪酸降低了G6PD前体mRNA的剪接速率, 基因的转录活性不受调节。该项目的总体目标是 了解这种受调控的剪接的分子机制。的目的 本申请的目的是定义参与这种调节的剪接调节蛋白, G6PD剪接和多不饱和脂肪如何抑制其活性。核心假设 G6PD外显子12的剪接调控区含有 并置的剪接沉默和增强元件。hnRNP K和/或hnRNP K的结合可以通过以下方式进行: L与沉默子的结合排除了剪接激活蛋白与增强子的结合。 多不饱和脂肪酸通过以下方式调节剪接调节蛋白的活性 翻译后修饰和/或核丰度。尽管普遍存在对 由于剪接的调控,人们对调控这一过程的细胞内信号知之甚少。 我们的实验是第一个描述抑制剪接作为一种机制, 多不饱和脂肪抑制基因表达。因此, 目前的建议将提供关于剪接压力调节的新数据,并定义新的 营养物质调节基因表达的途径。

项目成果

期刊论文数量(0)
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LISA M SALATI其他文献

LISA M SALATI的其他文献

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{{ truncateString('LISA M SALATI', 18)}}的其他基金

Nutrient Control of Gene Expression & Cell Signaling
基因表达的营养控制
  • 批准号:
    7603062
  • 财政年份:
    2005
  • 资助金额:
    $ 27.33万
  • 项目类别:
Nutrient Control of Gene Expression & Cell Signaling
基因表达的营养控制
  • 批准号:
    7232760
  • 财政年份:
    2005
  • 资助金额:
    $ 27.33万
  • 项目类别:
Nutrient Control of Gene Expression & Cell Signaling
基因表达的营养控制
  • 批准号:
    7406065
  • 财政年份:
    2005
  • 资助金额:
    $ 27.33万
  • 项目类别:
REGULATION OF GENE EXPRESSION BY DIETARY FAT
膳食脂肪对基因表达的调节
  • 批准号:
    2146176
  • 财政年份:
    1993
  • 资助金额:
    $ 27.33万
  • 项目类别:
REGULATION OF GENE EXPRESSION BY DIETARY FAT
膳食脂肪对基因表达的调节
  • 批准号:
    2146177
  • 财政年份:
    1993
  • 资助金额:
    $ 27.33万
  • 项目类别:
REGULATION OF GENE EXPRESSION BY DIETARY FAT
膳食脂肪对基因表达的调节
  • 批准号:
    6380816
  • 财政年份:
    1993
  • 资助金额:
    $ 27.33万
  • 项目类别:
Regulation of Gene Expression by Dietary Fat
膳食脂肪对基因表达的调节
  • 批准号:
    6741479
  • 财政年份:
    1993
  • 资助金额:
    $ 27.33万
  • 项目类别:
Regulation of Gene Expression by Dietary Fat
膳食脂肪对基因表达的调节
  • 批准号:
    7578716
  • 财政年份:
    1993
  • 资助金额:
    $ 27.33万
  • 项目类别:
REGULATION OF GENE EXPRESSION BY DIETARY FAT
膳食脂肪对基因表达的调节
  • 批准号:
    2146178
  • 财政年份:
    1993
  • 资助金额:
    $ 27.33万
  • 项目类别:
REGULATION OF GENE EXPRESSION BY DIETARY FAT
膳食脂肪对基因表达的调节
  • 批准号:
    2859204
  • 财政年份:
    1993
  • 资助金额:
    $ 27.33万
  • 项目类别:

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