METABOLIC REGULATION OF APO B MRNA EDITING

肝脏合成和分泌载脂蛋白B(Apo B)是 受饮食和荷尔蒙因素的代谢调节。最近的证据 表明饮食和激素调节了一种新的RNA加工形式 这就是所谓的信使核糖核酸编辑。编辑后的载脂蛋白B mRNA翻译成较低的 谷氨酰胺转化产生的分子量蛋白质(载脂蛋白B-L) 通过特定的单个碱基更改将密码子转换为框架内终止密码子 2153位密码子胞苷到尿苷(CAA-&GT；UAA)。大分子组装 参与信使核糖核酸的编辑(编辑小体)最近在 并建议在体外进行特异性的C-GT；U转化。 载脂蛋白B基因亚克隆的核糖核酸探针。RNA编辑与27s编辑小体 具有识别、组装和催化的特性 可见于许多其他依赖核糖核蛋白的过程。 已经提出了免疫学、分子和生化技术。 用于提纯编辑小体，表征其大分子组成 以及确定RNA识别和核苷酸的潜在机制 转换。针对编辑体组分的单抗 将生产和开发用于定性和免疫分析的 结构和功能的定量分析。这些研究将是 辅以使用突变体的编辑特异性的分子分析 Apo B mRNA构建，主要集中在编辑位点两侧的序列上。 对组织特异性特征的描述可能是 肝脏和肠道编辑活动的数量差异 也将接受评估。 这项拟议研究的意义在于它有可能 描述在载脂蛋白B产生水平上的代谢调节 信使核糖核酸的编辑机制及其合成的特定大分子 和/或交互参与控制。评选结果 拟议的研究对肝脏生产的影响 低密度脂蛋白(未编辑的载脂蛋白B)和乳糜粒的肠道生产(编辑 载脂蛋白B)相对于这些物质的可变致动脉粥样硬化潜能 人类体内的脂蛋白组份。此外，在中国获得的信息 这些研究将是重要的评估类属属性 信使核糖核酸编辑和识别其他可能作为编辑的信使核糖核酸 底物。

Hepatic synthesis and secretion of apolipoprotein B (apo B) is metabolically regulated by dietary and hormonal factors. Recent evidence suggests that diet and hormones regulate a novel form of RNA processing known as mRNA editing. Edited apo B mRNA translates into a lower molecular weight protein (apo B -L) due to the conversion of a glutamine codon to an in-frame stop codon through a specific single base change of cytidine to uridine in codon 2153 (CAA->UAA). Macromolecular assemblies involved in mRNA editing (editosomes) have been recently identified in vitro and proposed to carry out the specific C->U conversion on riboprobes of apo B cDNA subclones. RNA editing and the 27S editosome have characteristic properties of recognition, assembly and catalysis seen with many other ribonucleoprotein-dependent processes. Immunological, molecular and biochemical techniques have been proposed for purifying editosomes, characterizing their macromolecular composition and determining the mechanism underlying RNA recognition and nucleotide conversion. Monoclonal antibodies specific for the editosome components will be produced and immunoassays developed for qualitative and quantitative analyses of structure and function. These studies will be complemented by molecular analysis of editing-specificity using mutant apo B mRNA constructs which focus on sequences flanking the editing site. Description of tissue-specific characteristics which might underlie the quantitative differences in editing activity seen in liver and intestine will also be evaluated. The significance of the proposed research lies in its potential to describe metabolic regulation of apo B production at the level of the mechanism of mRNA editing and the specific macromolecules whose synthesis and/or interactions participate in the control. The results of the proposed studies have implications regarding the hepatic production of LDL (unedited apo B) and intestinal production of chylomicrons (edited apo B) with respect to the variable atherogenic potential of these lipoprotein fractions in humans. Moreover, the information obtained in these studies will be important for evaluating the generic properties of mRNA editing and identifying other mRNAs which might serve as editing substrates.