Translational Control of Apolipoprotein B mRNA

我们建议研究脂肪代谢中重要的蛋白质的生物化学和细胞生物学。人的肝脏分泌大量被称为“载脂蛋白”的蛋白质，这些蛋白质是形成被称为“脂蛋白”的脂肪颗粒所必需的。人体肝脏脂蛋白的分泌和代谢对维持血浆脂肪和胆固醇水平非常重要。我们对调节这些蛋白质的合成和分泌的基本分子和细胞机制感兴趣。在过去的几年里，我们的实验室一直在研究这些机制，并在载脂蛋白B合成的调控方面进行了一些重要的观察。我们现在建议继续这些研究，以进一步阐明关键的翻译调控机制。 细胞通过表达自己的基因并制造称为“信使”的中间信使分子来合成蛋白质。将信使核糖核酸信息转化为蛋白质分子是蛋白质表达调控的重要步骤。我们计划用一系列的实验来研究载脂蛋白B编码的信使核糖核酸的翻译。我们将研究结合该信使核糖核酸并调节其翻译过程的细胞因素。信使核糖核酸某些区域内的结构元素可能与细胞内的某些蛋白质相互作用。参与控制apoB mRNA翻译的蛋白质因素将在未来几年内进行研究。我们还将研究称为mRNPs的RNA-蛋白质复合体以及称为RNA颗粒的特殊细胞颗粒的作用。这些复合体似乎存储了受抑制的mRNA分子，这些分子可能在代谢刺激下释放出来，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人类肝脏合成载脂蛋白特别是载脂蛋白B的细胞机制。这些结果将有助于增进我们对细胞如何控制其蛋白质合成和表达的基本知识。

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.