Post-transcriptional Control of Immunoglobulin Expression

免疫球蛋白表达的转录后控制

• 批准号: 9106130
• 负责人: Martha Peterson
• 金额: $ 40.4万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9106130&HistoricalAwards=false
• 关键词: Post; transcriptional; Control; Immunoglobulin; Expression

Regulated transcriptional termination and RNA processing of the immunoglobulin (Ig) heavy chain gene during B cell development will be examined. The long-term goal of this research is to understand the general mechanisms governing these events as well as to determine the basis for the developmentally regulated changes that occur during B cell maturation. Transcriptional termination of normal and altered Ig u-o genes, introduced into established B and plasmacytoma cell lines, will be analyzed using the standard nuclear run-on assay or a proposed PCR-based assay. The contribution a functional poly (A) site and the downstream termination region make to termination within the u-o gene will be analyzed by deleting the poly (A) sites, altering the poly (A) site strength and mutating the termination region sequences. To determine whether the regulated production of us and um RNA, which is dependent on the efficiencies of two competing RNA processing reactions, is a u gene-specific event or is instead due to global changes in processing efficiencies, a non-Ig gene that can be alternatively processed by splicing and polyadenylation will be expressed in B and plasmacytoma cells. The u gene will be expressed in non-B cells to identify the non-regulated processing pathway and, by inference, the regulated pathway. The results from this study could have significant impact in other systems where alternatively processed pre-mRNAs are invoked as well as increasing our insight into the switching process in immunoglobin maturation.***//

转录终止和RNA加工的调控 在B细胞发育过程中免疫球蛋白（IG）重链基因将 接受检查。 这项研究的长期目标是了解 管理这些事件的一般机制，以及 确定发展监管变化的基础， 发生在B细胞成熟期间。 的转录终止 正常和改变的IG u-o基因，导入已建立的B， 浆细胞瘤细胞系，将使用标准品 核连续测定或提议的基于PCR的测定。 的 贡献功能性poly（A）位点和下游 在u-o基因内终止的终止区将是 通过删除poly（A）位点，改变poly（A）位点， 增强和突变终止区序列。 到 确定我们和um RNA的调节产生， 依赖于两种竞争性RNA加工的效率 反应，是一个u基因特异性事件，或者是由于全球 处理效率的变化，一个非免疫球蛋白基因， 或者通过剪接和多聚腺苷酸化进行加工， 在B和浆细胞瘤细胞中表达。 u基因将会是 在非B细胞中表达，以确定非调节加工 途径，并通过推理，调节途径。 这项研究的结果可能会对其他领域产生重大影响。 也调用了替代加工的前mRNA的系统 增加了我们对转换过程的了解， 免疫球蛋白成熟。*//