The relation of protein synthesis regulation and RNA metabolism

The mechanism for regulating protein synthesis in mammalian cells appears to be fundamentally different from that in bacteria. The protein synthesis system of bacteria is largely regulated by the supply of a short lived messenger RNA and is thus controlled at the level of transcription. In contrast, the messenger RNA of mammalian cells is very long lived and thus does not appear to vary in amount in response to different demands for protein synthesis. There appears to be a fundamental control system operating at the level of the initiation of translation. Cells can respond to depressed rates of protein synthesis by producing a factor which promotes the association of ribosomes with messenger RNA. This is demonstrated by inhibiting the initiation of translation at elevated temperatures. The cell response, which corrects the lesion, is inhibited by actinomycin but not by cycloheximide. Incubation in cycloheximide alone apparently induces the factor and makes cellular protein synthesis resistant to high temperature. The production of a factor stimulating initiation is demonstrated in vitro. Prior incubation of cells in cycloheximide leads to greatly enhanced rates of initiation in extracts obtained from those cells. Since the cell response is inhibited by actinomycin but induced by cycloheximide, it is concluded that the factor promoting initiation may be RNA.