EFFECTS OF FLUOROPYRIMIDINE ON RNA STRUCTURE & FUNCTION

我们已经评估了5-氟尿嘧啶引起的RNA改变。 我们 已经明确鉴定了mRNA和rRNA加工的变化。 我们 结果表明，5-氟尿嘧啶作用的可能位点是来自 在SnRNA中的掺入。 这些小分子量的富含尿嘧啶的RNA是 在较大的RNA的加工过程中， 细胞质mRNA和rRNA的前体。 我们计划继续工作， RNA代谢的区域。 将使用两种碱基类似物， 6-硫鸟嘌呤和5-氟尿嘧啶，嘌呤和嘧啶。 我们有 建立了评估二氢叶酸还原酶mRNA的方法， cMyc mRNA转录物和某些氮子的特异性探针将被 用于更清楚地描绘mRNA形成到成熟的 form. 此外，各种SnRNA对这些核RNA的影响 将评估处理步骤。 成熟的RNA 也将被研究。 这是一 基因控制的基因组外位点，我们发现， 暗示药物作用的部位。 虽然我们会在临床上使用 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.