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

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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 p70S6k/85S6k 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.