Differential Expression of the Murine Eukaryotic Translation Initiation Factor Isogenes eIF4AIand eIF4AIIIs Dependent upon Cellular Growth Status

The murine translation initiation factor eIF4A is encoded by two genes: eIF4AI, expressed in all mouse tissues, and eIF4AII, a gene preferentially expressed in organs with low proliferative capacity. To investigate the hypothesis that regulation of the eIF4A isogenes is dependent upon cellular growth status, steady state expression of eIF4AIand eIF4AIImRNAs was quantitated in asynchronous cell populations and in cultures synchronized by nutrient starvation. Our data showed that changes in cell growth state were responsible for striking differences in eIF4A isogene-specific regulation. eIF4AImRNA was 10-fold more abundant than eIF4AIIin growing cells. In growth arrested cells eIF4AImRNA levels remained unchanged, whereas eIF4AIImRNA levels increased approximately 3-fold. Following serum stimulation of growth arrested cells, eIF4AImRNA levels increased 3- to 10-fold; conversely, eIF4AIImRNA levels decreased 2- to 3-fold. Thus, eIF4AImRNA is synthesized and translated most efficiently in growing cells while eIF4AIImRNA synthesis and translation is associated preferentially with the growth-arrested (quiescent) state. This difference in expression patterns likely enables the cell to maintain required levels of this factor throughout its life cycle.