MESSENGER RNA DECAY IN MAMMALIAN CELLS

这些研究将集中在阐明原癌基因mRNA 在哺乳动物细胞中降解。 这些研究的目标是 以确定RNA的结构特征，负责 生长因子诱导的c-fos原癌基因的易感性 转录本，以确定这些不稳定性的机制 决定因素在mRNA衰变中起作用，并表征 进行这一过程的细胞质因子。 主 实验方法将涉及创建定义 突变和融合的c. fos基因，体外，导入 这些改变的基因构建体进入小鼠成纤维细胞， 分析所得mRNA转录物在体内的衰变。 细胞mRNA降解因子的表征将涉及 牙齿检查c-fos mRNA衰变的细胞处理了各种 刺激细胞生长和纯化这些降解的试剂 来自细胞质提取物的因子。 这些研究的结果 应该能增进我们对基因基本方面的了解， 这一表达目前还不太清楚，应该 有助于我们的长期目标， 在真核生物中控制mRNA衰变的原理。 此外，这些知识最终应该对以下方面有价值： 了解肿瘤发生的生物学机制。

These investigations will focus on elucidating proto-oncogene mRNA degradation in mammalian cells. The goal of these studies will be to identify the RNA structural features responsible for the liability of the growth factor-inducible c-fos proto-oncogene transcript to determine the mechanism(s) by which these instability determinants function in mRNA decay, and to characterize the cytoplasmic factors that carry out this process. The primary experimental approach to be employed will involve creating defined mutations and fusions of the c. fos gene in vitro, introducing these altered genetic constructs into mouse fitroblasts, and analyzing the decay of the resulting mRNA transcripts in vivo. Characterization of cellular mRNA degradation factors will involve tooth examining c-fos mRNA decay in cells treated with various agents that stimulate cell growth and purifying these degradation factors from cytoplasmic extracts. The results of these studies should enhance our knowledge of a fundamental aspect of gene expression that presently is poorly understood and should contribute to our long-term objective of defining the basic principles that govern mRNA decay in eukaryotic organisms. Moreover, this knowledge should ultimately be of value to understanding biological mechanisms of oncogenesis.