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DEVELOPMENTAL REGULATION AND PROCESSING OF RIBOSOMAL RNA

核糖体 RNA 的发育调控和加工

基本信息

批准号：
2458091
负责人：
BRIAN K ADLER
金额：
$ 8.96万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
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 1998-07-31
项目状态：
已结题

项目摘要

RNA processing and stability represent two post-transcriptional mechanisms by which gene expression may be regulated. With processing, sequences can be altered, targeting signals added, protein binding regions created, and functional activities changed. The importance of RNA processing is illustrated by beta-thalasemia in which an aberration produces a disease state. Similarly, modifications in RNA stability can have profound effects on gene expression. Some oncogene, growth factor, and cytokine mRNAs appear to contain signals which define their relatively short half-lives under normal conditions. However, their mRNA stability can apparently be altered, and it has been found to be prolonged in some cases in which increased gene expression would be expected. A prolongation of c-myc mRNA half-life has been noted in lymphoma, and the cytokine mRNAs have decreased degradation following T-cell stimulation. These examples suggest that mRNA processing and stability effect expression, but in general, they are poorly understood means of post-transcriptional gene regulation. A system in which post-transcriptional RNA modification and stability are known to be factors has been selected. Trypanosome mitochondria have unusual 3' end processing and regulation of their rRNAs. Investigations of the mechanisms by which these are achieved will permit further definition of the mechanisms involved in this form of post-transcriptional gene control. The research will focus on: l) delineation of the mechanism of 3' terminus formation by developing an in vitro system and defining the requirements for processing activity; 2) determination of the mechanism of variable rRNA stability and evaluation of any role 3' terminus formation may have in rRNA stability through degradation, gel shift mobility, and endonuclease protection studies. This work may improve our understanding of the process of post-transcriptional regulation of gene expression. Knowledge of such a fundamental process could give insight into the mechanisms involved in cell growth and differentiation.

RNA加工和稳定性代表了两种转录后机制基因的表达可以通过它来调节。通过处理，序列可以改变，添加靶向信号，创建蛋白质结合区域，以及功能活动发生变化。RNA加工的重要性在于例如β-地中海贫血，其中异常产生疾病状态同样，RNA稳定性的改变也会产生深远的影响，对基因表达的影响一些癌基因、生长因子和细胞因子mRNA 似乎包含定义其相对较短半衰期的信号在正常情况下。然而，它们的mRNA稳定性显然可以改变，并已发现在某些情况下，预计基因表达会增加。 c-myc mRNA的延长在淋巴瘤中已经注意到半衰期，并且细胞因子mRNA具有减少T细胞刺激后的降解。这些示例表明mRNA加工和稳定性影响表达，但在一般来说，它们是很少了解的转录后基因的手段，调控一个系统，其中转录后RNA修饰和稳定性是已知的因素已被选定。锥虫线粒体具有不寻常的3'末端加工和调节其rRNA。调查实现这些目标的机制将允许进一步定义这种形式的转录后基因的机制控制本研究的主要内容包括：1）阐明3'端的作用机制; 通过开发体外系统并定义末端形成，加工活动的要求; 2）确定的机制，可变rRNA稳定性和3'末端形成的任何作用的评价可能通过降解、凝胶移动性和核酸内切酶保护研究。这项工作可以增进我们对基因表达的转录后调节过程。了解这样一个基本过程可以使我们深入了解参与细胞生长和分化的机制。