Amino Acid Activation for Protein Synthesis

Abstract

Amino acid activation, in addition to its important role as the 1st step in protein synthesis, has taken on a new dimension of importance in the regulation of other cellular processes. Amino acid activation is a required step in RNA synthesis in organisms with stringent control. Why this requirement does not operate in cells with relaxed control is not understood. It is possible that amino acid activation, although required for RNA synthesis, may not be the most proximal step in regulating RNA synthesis. It has been suggested that polysome integrity is essential for RNA synthesis. This is based on the observation that polysomes disaggregate upon amino acid starvation in stringent cells, but not in relaxed cells. Amino acid activation is required for the repression of the biosynthesis of histidine and valine. The discovery of the mechanism of this effect could provide valuable information concerning the general processes of repression. An increasing number of examples have been reported in which modifications in tRNA occur that lead to differences in coding. Probably tRNA will become recognized as an important control element at the translational level. For example, in the code as now understood, there are 6 codons for leucine and arginine, and multiple codons for other amino acids; but there is no information to tell if an organism is making use of all codons at any one time. The restriction of certain codons for specific events, for example during differentiation, will allow for a fine degree of control by restricting the use of iso-accepting tRNA''s for these special events. Transfer RNA has been regarded as a vehicle for the transport of the activated amino acid to the site of protein synthesis. However, the increasing number of detailed in-vestigations of tRNA shows that these molecules are complex and possess a highly ordered structure that can have several conformation-al forms. A number of new and improved methods for the purification of aminoacyl-RNA synthetases and for the separation of individual tRNA''s have been reported. Many of these methods are capable of producing pure enzymes and tRNA''s in large quantities. When these become available the nature of the specificity between a synthetase and its tRNA, the basis of species specificity (and sometimes lack of it), the conformational forms of tRNA and the regulation of the maintenance of the active form will be explained.