Ribosomal RNA precursor transcription in rat liver is not dependent on continuous synthesis of proteins

The effect of inhibition of protein synthesis by cycloheximide on rRNA precursor transcription in rat liver was analyzed. Two doses of the drug were studied: low, 5 mg/kg, and high, 20 mg/kg. Both doses of cycloheximide cause rapid, complete and continuous inhibition of protein synthesis. The low dose of the antibiotic does not alter the rRNA precursor transcription for at least 4 h, while the high dose, which is lethal to rats, leads gradually to suppression of rRNA precursor synthesis. It is shown that the high dose of cycloheximide causes profound changes in the metabolism of the free nucleotides and drastic inhibition of [14C]orotate and [32P]orthophosphate uptake into the pool of free nucleotides. It is supposed that the strong side-effects of cycloheximide, rather than the cessation of protein synthesis, are responsible for the observed inhibition of rRNA precursor synthesis. It is concluded that rRNA precursor transcription is not regulated by rapidly turning-over protein(s).