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  • Original Paper
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N-myc translation is initiated via an internal ribosome entry segment that displays enhanced activity in neuronal cells

Oncogene volume 20, pages 2664–2670 (2001)Cite this article

Abstract

Eukaryotic translation can be initiated either by a cap-dependent mechanism or by internal ribosome entry, a process by which ribosomes are directly recruited to structured regions of mRNA upstream of the initiation codon. We analysed the 5′ untranslated region (UTR) of the proto-oncogene N-myc, and demonstrated by transfections in a dicistronic vector system that it contains a potent internal ribosome entry segment (IRES). The IRES is similar in length to the c-myc IRES and the activities of these IRESs are comparable in non-neuronal cells. Transfections were also carried out in cell lines derived from neuroblastomas, in which N-myc is expressed, and in a neuronal precursor cell line. In these cells the N-myc IRES is up to seven times more active than that of c-myc, suggesting that neuronal-specific non-canonical trans-acting factors are used by the N-myc but not the c-myc IRES. N-myc expression is increased by gene amplification in many neuroblastomas, but this is the first example of a translational mechanism by which N-myc expression could be further increased. The discovery of an IRES that displays enhanced activity in neuronal cell lines has important potential as a tool for protein expression in neural tissue.

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References

  • Akiri G, Nahari D, Finkelstein Y, Le SY, Elroy-Stein O, Levi BZ . 1998 Oncogene 17: 227–236

  • Bernstein J, Sella O, Le S, Elroy-Stein O . 1997 J. Biol. Chem. 272: 9356–9362

  • Blackwood EM, Eisenman RN . 1991 Science 251: 1211–1217

  • Brodeur GM, Segar RC, Schwab M, Varmus HE, Bishop JM . 1984 Science 224: 1121–1124

  • Chagnovich D, Cohn SL . 1996 J. Biol. Chem. 271: 33580–33586

  • Coldwell MJ, Mitchell SA, Stoneley M, MacFarlane M, Willis AE . 2000 Oncogene 19: 899–905

  • Cornelis S, Bruynooghe Y, Denecker G, Van Huffel S, Tinton S, Beyaert R . 2000 Mol. Cell 5: 597–605

  • Créancier L, Morello D, Mercier P, Prats A-C . 2000 J. Cell Biol. 150: 275–281

  • Dang CV . 1999 Mol. Cell. Biol. 19: 1–11

  • Derrington EA, Lopez-Lastra M, Chapel-Fernandez S, Cosset FL, Belin MF, Rudkin BB, Darlix JL . 1999 Hum. Gene Ther. 10: 1129–1138

  • Henis-Korenblit S, Levy Strumpf N, Goldstaub D, Kimchi A . 2000 Mol. Cell Biol. 20: 496–506

  • Holcik M, Lefebvre C, Yeh C, Chow T, Korneluk RG . 1999 Nat. Cell Biol. 1: 190–192

  • Huez I, Creancier L, Audigier S, Gensac MC, Prats AC, Prats H . 1998 Mol. Cell Biol. 18: 6178–6190

  • Ibson JM, Rabbitts PH . 1988 Oncogene 2: 399–402

  • Jackson RJ, Hunt SL, Reynolds JE, Kaminski A . 1995 Curr. Top. Microbiol. Immunol. 203: 1–29

  • Katoh K, Sawai S, Ueno K, Kondoh H . 1988 Nuc. Acids Res. 16: 3589

  • Kohl NE, Legouy E, DePinho RA, Nisen PD, Smith RK, Gee CE, Alt FW . 1986 Nature 319: 73–77

  • Lutz W, Stohr M, Schurmann J, Wenzel A, Lohr A, Schwab M . 1996 Oncogene 13: 803–812

  • Lutz W, Fulda S, Jeremias I, Debatin KM, Schwab M . 1998 Oncogene 17: 339–346

  • Malynn BA, de Alboran IM, O'Hagan RC, Bronson R, Davidson L, DePinho RA, Alt FW . 2000 Genes Dev. 14: 1390–1399

  • Miller D, Dibbens J, Damert A, Risau W, Vadas M, Goodall G . 1998 FEBS Lett. 434: 417–420

  • Nanbru C, Lafon I, Audigier S, Gensac MC, Vagner S, Guez G, Prats AC . 1997 J. Biol. Chem. 272: 32061–32066

  • Nesbit CE, Tersak JM, Prochownik EV . 1999 Oncogene 18: 3004–3016

  • Pilipenko EV, Pestova TV, Kolupaeva VG, Khitrina EV, Poperechnaya AN, Agol VI, Hellen CUT . 2000 Genes Dev. 14: 2028–2045

  • Pozner A, Goldenberg D, Negreanu V, Le SY, Elroy-Stein O, Levanon D, Groner Y . 2000 Mol. Cell Biol. 20: 2297–2307

  • Pyronnet S, Pradayrol L, Sonenberg N . 2000 Mol. Cell 5: 607–616

  • Saito H, Hayday AC, Wiman K, Hayward WS, Tonegawa S . 1983 Proc. Natl. Acad. Sci. USA 80: 7476–7460

  • Schwab M, Alitalo K, Klempnauer KH, Varmus HE, Bishop JM, Gilbert F, Brodeur G, Goldstein M, Trent J . 1983 Nature 305: 245–248

  • Shea TB . 1994 Neuroreport 5: 797–800

  • Sivak LE, Pont-Kingdon G, Le K, Mayr G, Tai KF, Stevens BT, Carroll WL . 1999 Mol. Cell Biol. 19: 155–163

  • Stanton BR, Perkins AS, Tessarollo L, Sassoon DA, Parada LF . 1992 Genes Dev. 6: 2235–2247

  • Stein L, Itin A, Einat P, Skaliter R, Grossman Z, Keshet E . 1998 Mol. Cell Biol. 18: 3112–3119

  • Stoneley M, Paulin FEM, Le Quesne JPC, Chappell SA, Willis AE . 1998 Oncogene 16: 423–428

  • Stoneley M, Chappell SA, Jopling CL, Dickens M, MacFarlane M, Willis AE . 2000a Mol. Cell Biol. 20: 1162–1169

  • Stoneley M, Subkhankulova T, Le Quesne JPC, Coldwell MJ, Jopling CL, Belsham GJ, Willis AE . 2000b Nuc. Acids Res. 28: 687–694

  • Strickland S, Mahdavi V . 1978 Cell 15: 393–403

  • Sugiyama A, Miyagi Y, Shirasawa Y, Kuchino Y . 1991 Oncogene 6: 2027–2032

  • Thiele CJ, Reynolds CP, Israel MA . 1985 Nature 313: 404–406

  • Vagner S, Gensac MC, Maret A, Bayard F, Amalric F, Prats H and Prats AC . 1995 Mol. Cell. Biol. 15: 35–44

  • Zimmerman KA, Yancopoulos GD, Collum RG, Smith RK, Kohl NE, Denis KA, Nau MM, Witte ON, Toran-Allerand D, Gee CE, Minna JD, Alt FW . 1986 Nature 319: 780–783

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Acknowledgements

This work was funded by the BBSRC (advanced fellowship to AE Willis). CL Jopling holds an MRC studentship.

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  1. Department of Biochemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK

    Catherine L Jopling & Anne E Willis

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  1. Catherine L Jopling
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Jopling, C., Willis, A. N-myc translation is initiated via an internal ribosome entry segment that displays enhanced activity in neuronal cells. Oncogene 20, 2664–2670 (2001). https://doi.org/10.1038/sj.onc.1204404

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