Inhibition of protein synthesis stabilizes histone mRNA

Abstract

The inhibition of protein synthesis in exponentially growing S49 cells leads to a specific fivefold increase in histone mRNA in 30 min. The rate of transcription of histone mRNA, measured in intact or digitonin-permeabilized cells, is increased slightly, if at all, by cycloheximide inhibition of protein synthesis. Both approach-to-equilibrium labeling and pulse-chase experiments show that cycloheximide prolongs histone mRNA half-life from approximately 30 min to greater than 2 h. Histone mRNA made before the addition of cycloheximide becomes stable after the inhibition of protein synthesis, whereas removal of the inhibitor is followed by rapid degradation of histone mRNA. This suggests that the increased stability of histone mRNA during inhibition of protein synthesis results not from alteration of the structure of the mRNA, but from the loss of an activity in the cell which regulates histone mRNA turnover.