DIFFERENTIAL EXPRESSION OF THE MURINE EUKARYOTIC TRANSLATION INITIATION-FACTOR ISOGENES EIF4A(I) AND EIF4A(II) IS DEPENDENT UPON CELLULAR GROWTH STATUS

The murine translation initiation factor eIF4A is encoded by two genes : eIF4A(I), expressed in all mouse tissues, and eIF4A(II), a gene pref erentially expressed in organs with low proliferative capacity, To inv estigate the hypothesis that regulation of the eIF4A isogenes is depen dent upon cellular growth status, steady state expression of eIF4A(I) and eIF4A(II) mRNAs was quantitated in asynchronous cell populations a nd in cultures synchronized by nutrient starvation, Our data showed th at changes in cell growth state were responsible for striking differen ces in eIF4A isogene-specific regulation, eIF4A(I) mRNA was 10-fold mo re abundant than eIF4A(II) in growing cells. In growth arrested cells eIF4A(I) mRNA levels remained unchanged, whereas eIF4A(II) mRNA levels increased approximately 3-fold. Following serum stimulation of growth arrested cells, eIF4A(I) mRNA levels increased 3- to 10-fold; convers ely, eIF4A(II) mRNA levels decreased 2- to 3-fold. Thus, eIF4A(I) mRNA is synthesized and translated most efficiently in growing cells while eIF4A(II) mRNA synthesis and translation is associated preferentially with the growth-arrested (quiescent) state, This difference in expres sion patterns likely enables the cell to maintain required levels of t his factor throughout its life cycle. (C) 1997 Academic Press.