The effect of 5-fluorouridine (5-FU) treatment of cells on the splicin
g of pre-mRNA was determined using cellular extracts and splicing vitr
o. Nuclear extracts from control cells and cells treated with 5-FU wer
e prepared and used to splice pre-mRNAs in vitro. The drug treatment r
esulted in inhibition of cell growth but had little effect on RNA synt
hesis. The extracts from 5-FU-treated cells showed significant inhibit
ion of splicing. This inhibition was the result of reduced efficiency
and was not caused by a block at a specific step in the splicing pathw
ay. There were no observable changes in the levels or physical propert
ies of the small nuclear ribonucleoprotein particles that are essentia
l co-factors in the splicing process. The deficiency in splicing in th
e extracts from 5-FU-treated cells could be supplemented by the additi
on of complementary fractions from a control extract.