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  • Original Paper
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Translation of the human c-myc P0 tricistronic mRNA involves two independent internal ribosome entry sites

Oncogene volume 20, pages 4270–4280 (2001)Cite this article

Abstract

The human c-myc proto-oncogene is transcribed from four alternative promoters (P0, P1, P2, and P3) giving rise to mRNAs having 5′ leader sequences of various length. The c-myc P0 mRNA contains three open reading frames (ORFs), the last one encoding c-Myc1 and c-Myc2 proteins generated by alternative translation initiated at CUG and AUG codons. The middle ORF (MYCHEX1) and the 5′ ORF (ORF1) code for proteins 188 and 114 amino acids in length, respectively. We and others previously identified an internal ribosome entry site (IRES) in P0 and P2 c-myc mRNAs, promoting the cap-independent translation of c-Myc1 and c-Myc2. Here, we report the presence of a second IRES (named IRES1) promoting the cap-independent translation of MYCHEX1 in c-myc P0 mRNA. Using deletion analysis, we mapped an 80-nt region essential for IRES1 activity. c-myc P0 mRNA is thus the first eukaryotic polycistronic mRNA described for which translation initiation of two different open reading frames (MYCHEX1 and c-Myc1/c-Myc2) involves internal ribosome entry.

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Acknowledgements

We thank Drs Hervé Prats and Cyril Gueydan for helpful discussions and for revising the manuscript. We thank JG Patton for sending the anti-PTB antibody. This work was funded by the EC Biotech Program (BIO4-CT95-0045), the Fund for Medical Scientific Research (Belgium, grant 3.4586.93), and the ‘Actions de Recherches Concertées' (grant 94–99/181). C. Nanbru was supported by a ‘Télévie’ grant.

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Authors and Affiliations

  1. Laboratoire de Chimie Biologique, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, rue Profs Jeener et Brachet 12, 6041, Gosselies, Belgium

    Cécile Nanbru, Patrick Defrance, Georges Huez & Véronique Kruys

  2. INSERM U397, Endocrinologie et Communication Cellulaire, Institut Louis Bugnard, CHU Rangueil, 31403 Toulouse Cedex 04, France

    Anne-Catherine Prats

  3. Laboratoire de Microbiologie, Université Libre de Bruxelles, avenue E Gryson, 1, Bruxelles, 1070, Belgium

    Louis Droogmans

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  1. Cécile Nanbru
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Correspondence to Véronique Kruys.

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Nanbru, C., Prats, AC., Droogmans, L. et al. Translation of the human c-myc P0 tricistronic mRNA involves two independent internal ribosome entry sites. Oncogene 20, 4270–4280 (2001). https://doi.org/10.1038/sj.onc.1204548

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