INDUCERS OF ERYTHROLEUKEMIC DIFFERENTIATION CAUSE MESSENGER-RNAS THATLACK POLY(A)-BINDING-PROTEIN TO ACCUMULATE IN TRANSLATIONALLY INACTIVE, SALT-LABILE 80-S-RIBOSOMAL COMPLEXES

Translation has an established role in the regulation of cell growth, Posttranslational modification of translation initiation and elongatio n factors or regulation of mRNA polyadenylation represent common means of regulating translation in response to mitogenic or developmental s ignals. Induced differentiation of Friend virus-transformed erythroleu kemia cells is accompanied by a rapid decrease in the translation rate of these cells. Although inducers do not alter initiation factor modi fications, characterization of their effect on mRNA translation provid es evidence that this is mediated by the poly(A)-binding protein (PABP ). Inducer exposure results in an increase in the amount of mRNA that sediments at 80 S and a decrease in the amount in polysomes, Although these 80 S ribosomes have characteristics previously attributed to ''v acant ribosomal couples,'' including lability in 500 mM KCl and an ina bility to incorporate amino acids into protein, we provide evidence th at these 80 S complexes are not vacant but contain mRNA that is stably bound to the 40 S subunit, whereas the 60 S subunit is dissociated fr om the complex by high salt. The absence of eukaryotic initiation fact or 2 from these complexes suggests that translation has proceeded thro ugh subunit joining, Immunoblotting demonstrates that the mRNAs in the se 80 S ribosomal complexes do not contain bound PABP and that this pr otein is found to be almost exclusively associated with translating po lysomes. These data suggest that the PABP plays a role in the accumula tion of these 80 S ribosomal mRNA complexes and may facilitate the for mation of translationally active salt-stable ribosomes.