Effects of 5-fluorouracil on the formation of modified nucleosides in yeast transfer RNA.
Yeast cells grown in the presence of the drug FUra synthesize RNA in which Urd is partially replaced by FUrd. Transfer RNAs in which 1.5-50% of the Urd has been replaced by FUrd have been isolated and their base compositions measured to determine the effect of FUrd incorporation on posttranscriptional nucleoside modification. This replacement results in an extensive reduction in the amounts of Thd, H56Urd and psird found in mature tRNA. Quantitatively, the reduction of psird greater than or equal to Thd greater than H56Urd. The losses of psird, Thd and H56Urd are greater than can be accounted for by the stoichiometry of FUrd incorporation. The formation of 5-MeCyd is not affected by the drug, whereas the methylated purines show substoichiometric losses in FUrd-containing tRNAs. In Escherichia coli, we have not observed any effects of FUra on the methylated purine content, although the effects on psird, Thd and H56Urd are similar. These findings indicate that (a) in both pro- and eukaryotic systems the enzymes responsible for psird, Thd and H56Urd formation are affected by FUra treatment in a similar manner; (b) prokaryotic purine methylases may be more tolerant of structural aberrations resulting from FUrd incorporation than eukaryotic methylases and (c) different methylases within one system show different sensitivities as shown by those responsible for 1-MeAdo and 5-MeCyd formation.
D001482:Base Composition / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D012331:RNA, Fungal / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D012331:RNA, Fungal; D012343:RNA, Transfer; D005472:Fluorouracil