EFFECTS OF FLUOROPYRIMIDINE ON RNA STRUCTURE & FUNCTION

我们评价了5-氟尿嘧啶对RNA的影响。我们 已经特别确定了mRNA和rRNA加工的变化。我们的 结果表明，5-氟尿嘧啶的作用部位可能来自 在单链RNA中掺入。这些富含尿嘧啶的小分子RNA是 在处理较大的RNA的过程中的各种步骤所需的 胞质mRNA和rRNA的前体。我们计划继续在 核糖核酸新陈代谢的这个区域。将使用两个碱基类比， 6-硫代鸟嘌呤和5-氟尿嘧啶，一种嘌呤和一种嘧啶。我们有 建立了二氢叶酸还原酶基因表达的检测方法 CMYC。MRNA转录本和某些硝基的特定探针将是 用来更清楚地描绘从mRNA形成到成熟的过程 形式。此外，不同的SnRNA对这些核RNA的影响 将对处理步骤进行评估。成熟的RNA通过什么机制 被运输到细胞质也将被研究。这是一个 基因控制的基因组外位置，我们的发现是 使人联想到毒品活动的场所。尽管我们将在临床上使用 可用的碱基类似物，结果将提供更好的理解 我们在RNA新陈代谢这一独特领域的知识。

We have evaluated the alterations induced in RNA by 5-fluorouracil. We have specifically identified changes in mRNA and rRNA processing. Our results indicate that a likely site of 5-fluorouracil action is from incorporation in SnRNA. These small molecular weight uracil rich RNA's are required for various steps in the processing of the larger RNA which are the precursors to cytoplasmic mRNA and rRNA. We plan to continue work in this area of RNA metabolism. Two base anologues will be used, 6-Thioguanine and 5-fluorouracil, a purine and a pyrimidine. We have established the methods for evaluating mRNA for dihydrofolate reductase and cMyc. Specific probes for the mRNA transcript and certain nitrons will be used to more clearly delineate the process of mRNA formation to the mature form. In addition, the effects of the various SnRNA's on these nuclear RNA processing steps will be evaluated. The mechanism by which the mature RNA is transported to the cytoplasm will be studied also. This is an extragenomic site of gene control which we have findings which are suggestive of a site for drug action. Although we will use clinically available base analogues, the results will provide a better understanding of our knowledge in this unique area of RNA metabolism.