The inhibition of nuclear RNA synthesis by the rifampicin derivative AF/013 in living cells.
The rifampicin derivative, AF/013, completely inhibits synthesis of the nucleolar and chromosomal RNA in explanted salivary gland cells of Chironomus tentans. When the glands are preincubated in rifampicin AF/013 for a short period before the addition of the radioactive precursors, labelling of RNA is depressed in all size classes to the same extent. In contrast, if rifampicin is replaced by the nucleoside analogue, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, a tentative initiation inhibitor of heterogeneous nuclear RNA, the label is reduced preferentially in the lower molecular weight region of the heterogeneous nuclear RNA spectrum. In chase type experiments, when rifampicin AF/013 is added after an initial labelling period, the synthesis of heterogeneous nuclear RNA is suppressed equally in all size classes, a result analogous to that obtained with the elongation inhibitor, alpha-amanitin. 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole, under similar chase conditions, preferentially inhibits the labelling of smaller heterogeneous nuclear RNA molecules, but later on abolishes labelling of molecules with higher S values, also. Rifampicin AF/013 prevents or affects seriously the normal processing of the prelabelled preribosomal RNA in the nucleolus. It further interferes with the export of nuclear RNA to the cytoplasm, and/or promotes a non-physiological breakdown of cytoplasmic RNA. The experimental data suggest that rifampicin AF/013 acts on RNA synthesis in living cells by interference with chain elongation.
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004175:Diptera; D004591:Electrophoresis, Polyacrylamide Gel; D012313:RNA / Q000096:biosynthesis*; D012293:Rifampin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012469:Salivary Glands / Q000378:metabolism
D012313:RNA; D012293:Rifampin