mRNA Specific Initiation Factors in the Control of Protein Synthesis

Abstract

Before mRNA was discovered it was commonly accepted that ribosomes in cells are specialized for the synthesis of specific proteins. Following the demonstration that the information for the amino acid sequence is, in fact, in the mRNA, ribosomes began to be viewed as non-specific organelles, capable of translating indiscriminately all information brought to them by mRNA. If this concept is true, all the controls of gene expression which must come into action when a cell adapts to new environmental conditions should be exclusively at the level of mRNA synthesis (transcription and maturation). To determine if translation control is at all a possible mechanism for the control of gene expression, it is therefore important to establish whether or not ribosomes are capable of discriminating between mRNAs and of translating preferentially one or another of the mRNAs present in the cytoplasm. This question is of course most relevant for mammalian cells, in which we know that (1) stable mRNAs function for prolonged periods of time (1) and (2) that more mRNA is synthesized in the nucleus than is actually translated on the cytoplasmic polyribosomes (see Scherrer, this volume). Since, however, the mechanism of protein synthesis is known in more detail in E.coli, we have concentrated much of our efforts in studying mRNA discrimination by E.coli ribosomes. Our experiments over the past three years have clearly demonstrated the existence of ribosome-associated protein factors which make the ribosome specialized for specific mRNAs. Recently, we have isolated similar factors from mammalian cells; these results will be presented in the second part of this paper.