Regulation of RNA polymerase II activity in a mutant rat myoblast cell line resistant to α amanitin

A MUTANT cell line, Ama102, resistant to the cytotoxic effects of a amanitin, the specific inhibitor of RNA polymerase II (refs 1 and 2), has been selected 3 from cultures of Yaffe's 4 rat skeletal muscle myoblast cell line, L 6 , treated with mutagen. Ama102 cells have similar doubling times for growth in the absence or presence of 3 μg ml −1 α amanitin whereas the Ama + parent does not survive in this concentration of α amanitin. Studies in vitro (ref. 3 and D.S. et al. , manuscript in preparation) indicate that Ama102 cells possess an RNA polymerase II which, retains about 30% of its activity in 0.1 μg ml −1 α amanitin, a concentration sufficient to inactivate completely the Ama + polymerase II. If α amanitin has a similar inhibitory action in vivo and in vitro , the normal growth of Ama102 cells in α amanitin coupled with the partial resistance of its RNA polymerase II activity to α amanitin in vitro seems paradoxical. Does the mutant Ama102 cell grow normally in α amanitin with only 30% of its normal RNA polymerase II active, or can the RNA polymerase II activity increase when the mutant is grown in α amanitin? The experiments reported here indicate that Ama102 cells can compensate for the partial inactivation of RNA polymerase II by α amanitin by increasing the RNA polymerase II activity.