Adriamycin inhibits human RH II/Gu RNA helicase activity by binding to its substrate

RNA helicases are enzymes important in RNA synthesis, processing, transport, and turnover. Human nucleolar RNA helicase II/Gu protein (RH II/Gu) was expressed in a baculovirus system. The purified recombinant RH II/Gu protein has RNA helicase activity on a 5' tailed ds RNA substrate in vitro. We found that Adriamycin, a widely used anticancer drug, inhibited RH II/Gu helicase activity in a dose-dependent manner with an IC(50) of 40 microM. Adriamycin bound to the RNA substrate, and the binding was disrupted by boiling or treatment with 1% SDS, suggesting that the binding of Adriamycin to RNA is reversible. Adriamycin was also found by gel electrophoresis to bind to yeast tRNA to form slow-migrating complexes. These results suggest that Adriamycin can inhibit RNA synthesis or processing by binding to RNA substrates.