Herrick D, Kufe D W
Mol Pharmacol. 1984 Jul;26(1):135-40.
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.
我们之前已经证明，5-氟尿嘧啶（FUra）掺入总细胞RNA与克隆存活能力丧失之间存在高度显著的关系。本研究通过证明FUra掺入核糖体前体核RNA（45S和32S）与致死性细胞事件之间的类似关系，扩展了这些发现。结果还表明，FUra掺入核糖体前体RNA（prRNA）的程度与成熟为细胞质28S和18S rRNA的抑制作用显著相关。这些发现表明，FUra掺入prRNA会改变参与45S和32S RNA加工的识别位点。我们发现RNase III对（FUra）prRNA的降解增强，进一步支持了这些数据，RNase III是一种与大肠杆菌prRNA和T7 mRNA成熟有关的酶。这些观察结果表明，FUra掺入prRNA是导致细胞质rRNA加工改变和细胞致死的原因。
