Nature, Vol.377, No.6547, 358-362, 1995
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 transcripts with different 5’ untranslated regions (5’UTRs) but identical coding 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, and a major 6.0-kb mRNA was untranslated and stored in a 100S ribonucleoprotein particle(3). Here we demonstrate that the 6.0-kb mRNA is selectively mobilized and translated in dispersed exponentially growing cells. Translational activation is prevented by rapamycin and mimicked by anisomycin, which suggests that translation of the 6.0-kb mRNA is regulated 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 regulated species.