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

Nature. 1995 Sep 28;377(6547):358-62. doi: 10.1038/377358a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisomycin / pharmacology
  • Cell Division / physiology*
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Polyenes / pharmacology
  • Protein Biosynthesis* / drug effects
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / genetics*
  • Ribosomal Protein S6
  • Ribosomal Proteins / metabolism
  • Sirolimus
  • Transfection
  • Tumor Cells, Cultured


  • Polyenes
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Ribosomal Protein S6
  • Ribosomal Proteins
  • Insulin-Like Growth Factor II
  • Anisomycin
  • Sirolimus