EFFECTS OF FLUOROPYRIMIDINE ON RNA STRUCTURE & FUNCTION

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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.