Growth-dependent translation of IGF-II mRNA by a rapamycin-sensitive pathway.
Insulin-like growth factor (IGF)-II is important for fetal growth and development. The human IGF-II gene generates multiple mature transcripts with different 5' untranslated regions (5'UTRs) but identical coding regions and 3'UTRs. 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. 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 prepro-IGF-II, whereas the major 6.0-kb mRNA provides a post-transcriptionally regulated species.
Nielsen
F C
FC
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen O, Denmark.
Ostergaard
L
L
Nielsen
J
J
Christiansen
J
J
D000841:Anisomycin / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D011090:Polyenes / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins / Q000378:metabolism; D020123:Sirolimus; D014162:Transfection; D014407:Tumor Cells, Cultured
D011090:Polyenes; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D007335:Insulin-Like Growth Factor II; D000841:Anisomycin; D020123:Sirolimus