Translational Control of Apolipoprotein B mRNA

载脂蛋白 B mRNA 的翻译控制

• 批准号: 41858-2012
• 负责人: Adeli, Khosrow
• 金额: $ 2.91万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=568867
• 关键词: Translational; Control; Apolipoprotein; mRNA

We are proposing to study the biochemistry and cell biology of proteins important in lipid metabolism. Human liver secretes a number of proteins called "apolipoproteins" which are essential for formation of lipid particles called "lipoproteins". Secretion and metabolism of lipoproteins by the human liver is very important in maintaining the plasma levels of fat and cholesterol. We are interested in the basic molecular and cellular mechanisms which regulate the synthesis and secretion of these proteins. Our laboratory has been studying these mechanisms for the past several years and has made a number of important observations on regulation of apolipoprotein B synthesis. We now propose to continue these investigations to further elucidate key translational control mechanisms. Cells synthesize proteins by expressing their genes and making intermediate messenger molecules called "mRNA". The translation of the information on mRNA into a protein molecule is an important step at which protein expression is regulated. We have proposed to use a series of experiments to study the translation of the mRNA coding for apolipoprotein B. We will investigate the cellular factors which bind the mRNA and regulate its translation process. Structural elements within certain regions of an mRNA may interact with certain proteins within the cell. The protein factors involved in control of apoB mRNA translation will be studied over the next few years. We will also study the role of RNA-protein complexes called mRNPs as well as special cell granules called RNA granules. These complexes appear to store suppressed mRNA molecules which may be released upon metabolic stimulation for translation and protein synthesis. The long-term objective of this research program is to elucidate the cellular mechanisms which regulate the synthesis of apolipoproteins particularly apolipoprotein B by the human liver. The results will be useful in advancing our basic knowledge of how cells control their protein synthesis and expression.

我们建议研究脂质代谢中重要蛋白质的生物化学和细胞生物学。人类肝脏分泌许多称为“载脂蛋白”的蛋白质，其对于形成称为“脂蛋白”的脂质颗粒是必需的。人类肝脏分泌和代谢脂蛋白对维持血浆中脂肪和胆固醇水平非常重要。我们对调节这些蛋白质合成和分泌的基本分子和细胞机制感兴趣。我们实验室在过去几年中一直在研究这些机制，并对载脂蛋白B合成的调节进行了一些重要的观察。我们现在建议继续这些调查，以进一步阐明关键的翻译控制机制。 细胞合成蛋白质的过程是通过表达它们的基因和制造中间信使分子（称为“mRNA”）。将mRNA上的信息翻译成蛋白质分子是调节蛋白质表达的重要步骤。我们已经提出了一系列的实验来研究载脂蛋白B的mRNA编码的翻译。我们将研究结合mRNA并调节其翻译过程的细胞因子。mRNA的某些区域内的结构元件可以与细胞内的某些蛋白质相互作用。在未来几年内，将研究参与apoB mRNA翻译控制的蛋白质因素。我们还将研究称为mRNP的RNA-蛋白质复合物以及称为RNA颗粒的特殊细胞颗粒的作用。这些复合物似乎储存了被抑制的mRNA分子，这些分子可能在代谢刺激时释放，用于翻译和蛋白质合成。 这项研究计划的长期目标是阐明调节载脂蛋白特别是载脂蛋白B合成的细胞机制。这些结果将有助于推进我们对细胞如何控制其蛋白质合成和表达的基础知识。