Alternative Translation of the Proto-oncogene c-mycby an Internal Ribosome Entry Site
| Autor: | Cécile Nanbru, Anne-Catherine Prats, Georges Huez, Stéphan Vagner, Marie-Claire Gensac, Isabelle Lafon, Sylvie Audigier |
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| Rok vydání: | 1997 |
| Předmět: |
Chloramphenicol O-Acetyltransferase
RNA Caps Five prime untranslated region Recombinant Fusion Proteins Molecular Sequence Data Genes myc Biology Proto-Oncogene Mas Biochemistry Eukaryotic translation Sequence Homology Nucleic Acid Eukaryotic initiation factor Tumor Cells Cultured Animals Humans Initiation factor RNA Messenger Ribosome profiling Codon Promoter Regions Genetic Molecular Biology Genetics Base Sequence EIF4E Cell Biology Ribosomal binding site Internal ribosome entry site Protein Biosynthesis COS Cells Nucleic Acid Conformation Ribosomes |
| Zdroj: | Journal of Biological Chemistry. 272:32061-32066 |
| ISSN: | 0021-9258 |
| Popis: | The human proto-oncogene c-myc encodes two proteins, c-Myc1 and c-Myc2, from two initiation codons, CUG and AUG, respectively. It is also transcribed from four alternative promoters (P0, P1, P2, and P3), giving rise to different RNA 5'-leader sequences, the long sizes of which suggest that they must be inefficiently translated by the classical ribosome scanning mechanism. Here we have examined the influence of three c-myc mRNA 5'-leaders on the translation of chimeric myc-CAT mRNAs. We observed that in the reticulocyte rabbit lysate, these 5'-leaders lead to cap-independent translation initiation. To determine whether this kind of initiation resulted from the presence of an internal ribosome entry site (IRES), COS-7 cells were transfected with bicistronic vectors containing the different c-myc 5'-leaders in the intercistronic region. An IRES was identified, requiring elements located within the P2 leader, between nucleotides -363 and -94 upstream from the CUG start codon. This is the first demonstration of the existence of IRES-dependent translation for a proto-oncogene. This IRES could be a translation enhancer, allowing activation of c-myc expression under the control of trans-acting factors and in response to specific cell stimuli. |
| Databáze: | OpenAIRE |
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