DEVELOPMENTAL REGULATION AND PROCESSING OF RIBOSOMAL RNA

核糖体 RNA 的发育调控和加工

• 批准号: 2100799
• 负责人: BRIAN K ADLER
• 金额: $ 7.88万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/2100799
• 关键词: RNA binding protein; RNase protection assay; Trypanosoma; acidity /alkalinity; chemical stability; developmental genetics; enzyme substrate; gel mobility shift assay; gene expression; genetic regulation; laboratory mouse; laboratory rat; magnesium; mitochondria; nucleic acid sequence; polymerase chain reaction; posttranscriptional RNA processing; ribosomal DNA; ribosomal RNA; ribosomal proteins

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处理和稳定性代表两个转录后机制 可以通过其中调节基因表达。通过处理，序列可以 改变，添加了靶向信号，创建蛋白质结合区域以及 功能活动改变了。 RNA处理的重要性是 由β-甲性贫血症插图，其中畸变会产生疾病 状态。同样，RNA稳定性的修改可能会产生深远的影响 关于基因表达。一些癌基因，生长因子和细胞因子mRNA 似乎包含信号，这些信号定义了他们相对较短的半衰期 在正常条件下。但是，它们的mRNA稳定性显然可以是 发生了变化，在某些情况下发现它延长了 预期基因表达增加。 c-myc mRNA的延长 半衰期已在淋巴瘤中注意到，细胞因子mRNA具有 T细胞刺激后降解降低。 这些例子 提示mRNA处理和稳定性效应表达，但在 一般，它们是鲜为人知的转录后基因手段 规定。 转录后RNA修饰和稳定性的系统 已知是因素。锥虫线粒体具有 不寻常的3'结束处理和对其RRNA的调节。调查 实现这些实现的机制将允许进一​​步定义 这种形式的转录后基因所涉及的机制 控制。该研究将重点介绍：l）3'机制的描述 通过开发体外系统并定义终端形成 处理活动的要求； 2）确定机制 可变rRNA稳定性和对任何角色的评估3'末端形成 可能通过降解，凝胶移动性和RRNA稳定性具有 核酸内切酶保护研究。这项工作可以提高我们的理解 基因表达的转录后调节过程。 对这种基本过程的了解可以洞悉 涉及细胞生长和分化的机制。