rRNA transcription initiation is decreased by inhibitors of the yeast cell cycle control step 'start'

Inhibitors of the 'start' regulatory step in the cell cycle of the yeast Saccharomyces cerevisiae are known by indirect studies to perturb RNA metabolism. We have investigated these effects further and show here by a pulse-labeling and quantitative hybridization procedure that pre-rRNA transcription was substantially decreased by five inhibitors of start but was transiently stimulated by the mating pheromone α-factor. Thus in contrast to the effects of the other start inhibitors, the inhibition of start by α-factor is unrelated to this aspect of biosynthetic activity. Mating factor treatment also stimulated the synthesis rate of poly(A)⁺ RNA. The start inhibitors o-phenanthroline and L-ethionine inhibited pre-rRNA transcription with little effect on poly(A)⁺ RNA synthesis rates. Northern analysis showed that all inhibitors of start also inhibited pre-rRNA transcript cleavage, a process that has been dissociated from the inhibition of start. Most inhibitors also affected ATP pool size. One inhibitor, o-phenanthroline, markedly induced the general control response.