Lethality associated with incorporation of 5-fluorouracil into preribosomal RNA.
We have previously demonstrated a highly significant relationship between incorporation of 5-fluorouracil (FUra) into total cellular RNA and loss of clonogenic survival. The present study extends these findings by demonstrating a similar relationship between incorporation of FUra into preribosomal nuclear RNA (45 S and 32 S) and lethal cellular events. The results also demonstrate that the extent of FUra incorporation into preribosomal RNA (prRNA) correlates significantly with inhibition of maturation to cytoplasmic 28 S and 18 S rRNA. These findings suggest that the incorporation of FUra into prRNA alters recognition sites involved in the processing of 45 S and 32 S RNA. These data are further supported by our finding of an enhanced degradation of (FUra)prRNA by RNase III, an enzyme implicated in the maturation of Escherichia coli prRNA and T7 mRNA. These observations suggest that the incorporation of FUra into prRNA is responsible for altered processing to cytoplasmic rRNA and cell lethality.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005472:Fluorouracil / Q000378:metabolism / Q000633:toxicity*; D007700:Kinetics; D007942:Leukemia, Experimental / Q000503:physiopathology*; D051379:Mice; D009694:Nucleic Acid Precursors / Q000096:biosynthesis*; D012322:RNA Precursors; D012335:RNA, Ribosomal / Q000096:biosynthesis*
D009694:Nucleic Acid Precursors; D012322:RNA Precursors; D012335:RNA, Ribosomal; D005472:Fluorouracil