Growth-dependent translation of IGF-II mRNA by a rapamycin-sensitive pathway

Abstract

INSULIN-LIKE growth factor (IGF)-II is important for fetal growth and development¹. The human IGF-II gene generates multiple mature transcripts with different 5′ untranslated regions (5′UTRs) but identical coding regions and 3′UTRs². 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 particle³. 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.