GROWTH-DEPENDENT TRANSLATION OF IGF-II MESSENGER-RNA BY A RAPAMYCIN-SENSITIVE PATHWAY

INSULIN-LIKE growth factor (IGF)-II is important for fetal growth and development(1). The human IGF-II gene generates multiple mature transc ripts with different 5' untranslated regions (5'UTRs) but identical co ding regions and 3'UTRs(2). We have previously shown that a minor 4.8- kilobase messenger RNA was engaged in the synthesis of preproIGF-II, a nd a major 6.0-kb mRNA was untranslated and stored in a 100S ribonucle oprotein particle(3). Here we demonstrate that the 6.0-kb mRNA is sele ctively mobilized and translated in dispersed exponentially growing ce lls. Translational activation is prevented by rapamycin and mimicked b y anisomycin, which suggests that translation of the 6.0-kb mRNA is re gulated by the p70(S6k)/85(S6k) kinase signalling pathway. Therefore, the minor 4.8-kb mRNA generates a constitutive production of preproIGF -II, whereas the major 6.0-kb mRNA provides a post-transcriptionally r egulated species.