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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.

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References

  1. Nielsen, F. C. Prog. Growth Factor Res. 4, 257–290 (1992).

    Article  CAS  Google Scholar 

  2. Sussenbach, J. S. Prog. Growth Factor Res. 1, 33–48 (1989).

    Article  CAS  Google Scholar 

  3. Nielsen, F. C., Gammeltoft, S. & Christiansen, J. J. biol. Chem. 265, 13431–13434 (1990).

    CAS  PubMed  Google Scholar 

  4. Jefferies, H. B. J., Thomas, G. & Thomas, G. J. biol. Chem. 269, 4367–4372 (1994).

    CAS  PubMed  Google Scholar 

  5. Nielsen, F. C. & Christiansen, J. J. biol. Chem. 267, 19404–19411 (1992).

    CAS  PubMed  Google Scholar 

  6. Jefferies, H. B. J., Reinhard, C., Kozma, S. C. & Thomas, G. Proc. natn. Acad. Sci. U.S.A. 91, 4441–4445 (1994).

    Article  ADS  CAS  Google Scholar 

  7. Terada, N. et al. Proc. natn. Acad. Sci. U.S.A. 91, 11477–11481 (1994).

    Article  ADS  CAS  Google Scholar 

  8. Chung, J., Kuo, C. J., Crabtree, G. R. & Blenis, J. Cell 69, 1227–1236 (1992).

    Article  CAS  Google Scholar 

  9. Price, D. J., Grove, J. R., Calvo, V., Avruch, J. & Bierer, B. E. Science 257, 973–977 (1992).

    Article  ADS  CAS  Google Scholar 

  10. Jenö, P., Jäggi, N., Luther, H., Siegmann, M. & Thomas, G. J. biol. Chem. 264, 1293–1297 (1989).

    PubMed  Google Scholar 

  11. Mahadevan, L. C. & Edwards, D. R. Nature 349, 747–748 (1991).

    Article  ADS  CAS  Google Scholar 

  12. Kardalinou, E., Zhelev, N., Hazzalin, C. A. & Mahadevan, L. C. Molec. cell. Biol. 14, 1066–1074 (1994).

    Article  CAS  Google Scholar 

  13. Avni, D., Shama, S., Loreni, F. & Meyuhas, O. Molec. cell. Biol. 14, 3822–3833 (1994).

    Article  CAS  Google Scholar 

  14. De Moor, C. H. et al. Biochem. J. 307, 225–231 (1995).

    Article  CAS  Google Scholar 

  15. Ballou, L. M., Luther, H. & Thomas, G. Nature 349, 348–350 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Chung, J., Grammer, T. C., Lemon, K. P., Kazlauskas, A. & Blenis, J. Nature 370, 71–75 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Ming, X.-F. et al. Nature 371, 426–429 (1994).

    Article  ADS  CAS  Google Scholar 

  18. Thomas, G., Martin-Pérez, J., Siegmann, M. & Otto, A. M. Cell 30, 235–242 (1982).

    Article  CAS  Google Scholar 

  19. Myers, M. G. Jr et al. J. biol. Chem. 269, 28783–28789 (1994).

    CAS  PubMed  Google Scholar 

  20. Ohlsson, R., Holmgren, L., Glaser, A., Szpecht, A. & Pfeifer-Ohlsson, S. EMBO J. 8, 1993–1999 (1989).

    Article  CAS  Google Scholar 

  21. Newell, S., Ward, A. & Graham, C. Molec. Reprod. Dev. 39, 249–258 (1994).

    Article  CAS  Google Scholar 

  22. El-Badry, O. M. et al. Cell Growth Differ. 1, 325–331 (1990).

    CAS  PubMed  Google Scholar 

  23. Dilling, M. B. et al. Cancer Res. 54, 903–907 (1994).

    CAS  PubMed  Google Scholar 

  24. Holthuizen, P., Van der Lee, F. M., Ikejiri, K., Yamamoto, M. & Sussenbach, J. S. Biochem. biophys. Acta. 1087, 341–343 (1990).

    CAS  PubMed  Google Scholar 

  25. Luckow, B. & Schutz, G. Nucleic Acids Res. 15, 5490 (1987).

    Article  CAS  Google Scholar 

  26. Chen, C. & Okayama, H. Molec. cell. Biol. 7, 2745–2752 (1987).

    Article  CAS  Google Scholar 

  27. An, G., Hidaka, K. & Siminovitch, L. Molec. cell. Biol. 2, 1628–1632 (1982).

    Article  CAS  Google Scholar 

  28. Herbomel, P., Bourachot, B. & Yaniv, M. Cell 39, 653–662 (1984).

    Article  CAS  Google Scholar 

  29. Siegmann, M. & Thomas, G. Meth. Enzym. 146, 362–369 (1987).

    Article  CAS  Google Scholar 

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Author notes

  1. Jan Christiansen: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Clinical Biochemistry, Rigshospitalet, DK-2100, Copenhagen Ø, Denmark

    Finn C. Nielsen

  2. Institute of Molecular Biology, University of Copenhagen, DK-1307, Copenhagen K, Denmark

    Lars Østergaard, Jacob Nielsen & Jan Christiansen

Authors
  1. Finn C. Nielsen
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  2. Lars Østergaard
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  3. Jacob Nielsen
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  4. Jan Christiansen
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Nielsen, F., Østergaard, L., Nielsen, J. et al. Growth-dependent translation of IGF-II mRNA by a rapamycin-sensitive pathway. Nature 377, 358–362 (1995). https://doi.org/10.1038/377358a0

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