DEVELOPMENTAL REGULATION AND PROCESSING OF RIBOSOMAL RNA

RNA加工和稳定性代表了两种转录后机制 它可以调节基因的表达。通过处理，序列可以 改变，添加靶向信号，创建蛋白质结合区，以及 功能活动已更改。RNA加工的重要性在于 由β-地中海贫血说明，在这种情况下，一个异常会导致一种疾病 州政府。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。某些癌基因、生长因子和细胞因子mRNAs 似乎包含定义它们相对较短的半衰期的信号 在正常情况下。然而，它们的信使核糖核酸的稳定性显然 已被更改，并且在某些情况下被发现延长 基因表达增加是意料之中的。C-myc基因表达的延长 淋巴瘤的半衰期已经被注意到，细胞因子mRNAs已经 T细胞刺激后降解减少。这些例子 提示信使核糖核酸的加工和稳定性影响表达，但在 一般说来，它们是一种鲜为人知的转录后基因手段 监管。 一种转录后RNA修饰和稳定性 已知的因素已被选定。锥虫线粒体有 不寻常的3‘端加工和它们的rRNA的调节。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涉及的机制 控制力。研究的重点是：L)勾画3‘的作用机制。 通过开发体外系统和定义 加工活动的要求；2)确定加工活动的机制 可变rRNA稳定性和任何角色3‘末端形成的评估 可能通过降解、凝胶移动和移动在rRNA中具有稳定性 核酸内切酶保护研究。这项工作可能会提高我们的认识 转录后基因表达调控的过程。 对这样一个基本过程的了解可以让我们深入了解 参与细胞生长和分化的机制。

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.