Biological Sciences: Specific Action of α-Amanitin on Mammalian RNA Polymerase Protein

Abstract

MOST inhibitors of RNA synthesis act on the DNA template rather than directly on the polymerizing enzyme. Antibiotics that inhibit RNA synthesis by binding to DNA include actinomycin D¹, miracil D², nogalomycin³, chromomycin A₃⁴, aflatoxin⁵, echinomycin, daunomycin, mithramycin and olivomycin⁶, ethidium bromide⁷, pro-flavine⁸, nitrogen mustard⁹ and acetylaminofluorene¹⁰. In each case tested, there is evidence that the antibiotic can inhibit RNA synthesis in both animal and bacterial cells, a finding to be expected because the site of the inhibitory action is the DNA template and not the enzyme. On the other hand, a few antibiotics are known to react with the enzyme molecule itself and these are more species selective. The bacterial polymerase but not the animal polymerase is inhibited by the rifamycins¹¹, streptovaricin¹² and probably streptolydigin¹³. Rifamycin has been shown to bind stoichiometrically to the bacterial enzyme molecule and to prevent initiation¹⁴, whereas streptolydigin appears to inhibit chain elongation¹³.