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Rapid and selective inhibition of RNA synthesis in yeast by 8-hydroxyquinoline.

A selective inhibitor of RNA synthesis is an essential tool for studies of the mechanisms of control of enzyme synthesis. Yeast is a particularly suitable organism for such studies, but until recently no suitable inhibitor of RNA synthesis has been available. 8-HydroxyquinolineY at concentrations of 10–50 μ;g/ml, rapidly and selectively inhibits RNA synthesis in fission yeast. Protein synthesis, cell growth and uridine uptake are not immediately affected. The mechanism of inhibition appears to be by chelation of divalent cations required for RNA synthesis. An explanation of the selectivity of inhibition is proposed. An estimate of 20 min for the upper limit of messenger RNA half-life was obtained by following the rate of protein synthesis after inhibition of RNA synthesis by 8-hydroxyquinoline. At low concentrations, 8-hydroxyquinoline inhibits the synthesis of ribosomal RNA and messenger RNA, but has no effect on the synthesis of transfer RNA or 5-S RNA. This differential effect could arise from differing divalent cation requirements of different RNA polymerases.