SYNTHESIS of proteins from the mRNA in eukaryotic cells differs from prokaryotes in two important ways. In the mammalian cell, the translation of mRNA in the cytoplasm is remote from the transcription in the nucleus, whereas in bacteria these two processes occur almost simultaneously1,2. Bacterial protein synthesis ceases within several minutes of inhibition of RNA transcription with actinomycin3; hence, the mRNA is short-lived. In metazoan eukaryotic cells, a similar experiment indicates that protein synthesis is not immediately affected by inhibition of transcription. Thus the mRNA is much more stable - of the order of several hours4. In a few specialized systems, the lifetime of mRNA can be deduced by observing the decay of protein synthesis after RNA synthesis has ceased. The messenger for haemoglobin in the reticulocyte5 and for silk fibroin in the silkworm6 are examples of stable messenger molecules with a lifetime of several days. The measurement of messenger lifetime in cells with active RNA metabolism is more difficult. In the experimental approach mentioned above, new RNA synthesis was blocked with actinomycin and the subsequent decay of protein synthesis measured. Under these conditions, protein synthesis generally decreased with a 2.5 to 3 h half-life in a wide variety of systems 4,7-9. Interpreting the decay of protein synthesis as due to a concomitant degradation of mRNA assumes that the availability of messenger molecules is limiting in protein synthesis. Here, we shall show that mRNA decay is not responsible for protein synthesis decay in actinomycin. Rather, mRNA appears quite stable after the administration of actinomycin. The subsequent decay of protein synthesis appears to be due to a failure in the initiation of translation.
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