Ribosome Formation is Blocked by Camptothecin, a Reversible Inhibitor of RNA Synthesis

Abstract

A new drug, camptothecin, has been used to study the regulation of ribosome synthesis in HeLa cells. 5 muM camptothecin inhibits the synthesis of heterogeneously sedimenting nuclear RNA by about 70%. Camptothecin also blocks a specific step in the processing of ribosomal precursor RNA, allowing the conversion of 45S RNA to 32S RNA, but inhibiting the conversion of 32S RNA to 28S RNA. The action of camptothecin, unlike that of actinomycin D, is rapidly reversible. Within 5 min after the removal of the drug, ribosomal precursor RNA synthesis and maturation resume at the normal rate. Ribosomal proteins made in the presence of camptothecin do not accumulate in the nucleolus, and are not subsequently used to form ribosomes if RNA synthesis is allowed to resume.