EXPRESSION OF INITIATION-FACTOR GENES IN MAMMALIAN-CELLS

This review focuses on how cells establish the levels of initiation fa ctors, within the broader context of determining levels of the transla tional machinery. Most initiation factor polypeptides are moderately a bundant proteins with concentrations approaching those of ribosomes. e IF4A and eIF5A are more abundant than ribosomes. whereas eIF4F alpha a nd eIF2B are considerably less abundant than the other factors. The cl oning of cDNAs generates hybridization probes for monitoring the level s and activities of factor mRNAs, and the cloning of their genes is ju st beginning to provide insight into promoter structures and regulatio n. Initiation factor gene expression appears to be coordinately regula ted in many cases, and preferential synthesis is seen. in mitogen-acti vated T-cells. The gene for eIF2 alpha has been best characterized, an d mechanisms that provide for the coordinated synthesis of eIF2 subuni ts are emerging. Recombinant DNA methods also allow investigators to m anipulate the levels of expression of specific factor genes by overexp ression or antisense repression. Such approaches provide a means to in vestigate in vivo the mechanisms of action of the initiation factors a nd their roles in regulating translation rates.