REGULATION OF PROTEIN-SYNTHESIS AT THE ELONGATION STAGE - NEW INSIGHTS INTO THE CONTROL OF GENE-EXPRESSION IN EUKARYOTES

There are many reports which demonstrate that the rate of protein biosynthesis at the elongation stage is actively regulated in eukaryotic cells. Possible physiological roles for this type of regulation are: the coordination of translation of mRNA with different initiation rate constants: regulation of transition between different physiological states of a cell, such as transition between stages of the cell cycle; and in general, any situation where the maintenance of a particular physiological state is dependent on continuous protein synthesis. A number of covalent modifications of elongation factors offer potential mechanisms for such regulation. Among the various modifications of elongation factors, phosphorylation of eEF-2 by the specific Ca2+/calmodulin-dependent eEF-2 kinase is the best studied and perhaps the most important mechanism for regulation of elongation rate. Since this phosphorylation is strictly Ca2+-dependent, and makes eEF-2 inactive in translation, this mechanism could explain how changes in the intracellular free Ca2+ concentration may regulate elongation rate. We also discuss some recent findings concerning elongation factors, such as the discovery of developmental stage-specific elongation factors and the regulated binding of eEF-1-alpha to cytoskeletal elements. Together, these observations underline the importance of the elongation stage of translation in the regulation of the cellular processes essential for normal cell life.