title: Analysis of the c-myc IRES; a potential role for cell-type specific trans-acting factors and the nuclear compartment.
abstract: The 5' UTR of c -myc mRNA contains an internal ribo-some entry segment (IRES) and consequently, c -myc mRNAs can be translated by the alternative mechanism of internal ribosome entry. However, there is also some evidence suggesting that c -myc mRNA translation can occur via the conventional cap-dependent scanning mechanism. Using both bicistronic and monocistronic mRNAs containing the c- myc 5' UTR, we demonstrate that both mechanisms can contribute to c- myc protein synthesis. A wide range of cell types are capable of initiating translation of c- myc by internal ribosome entry, albeit with different efficiencies. Moreover, our data suggest that the spectrum of efficiencies observed in these cell types is likely to be due to variation in the cellular concentration of non-canonical translation factors. Interestingly, the c -myc IRES is 7-fold more active than the human rhinovirus 2 (HRV2) IRES and 5-fold more active than the encephalomyocarditis virus (EMCV) IRES. However, the protein requirements for the c -myc IRES must differ significantly from these viral IRESs, since an unidentified nuclear event appears to be a pre-requisite for efficient c -myc IRES-driven initiation.
authors.affiliation: Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK.
authors.forename: M
authors.initials: M
authors.lastname: Stoneley
authors.forename: T
authors.initials: T
authors.lastname: Subkhankulova
authors.forename: J P
authors.initials: JP
authors.lastname: Le Quesne
authors.forename: M J
authors.initials: MJ
authors.lastname: Coldwell
authors.forename: C L
authors.initials: CL
authors.lastname: Jopling
authors.forename: G J
authors.initials: GJ
authors.lastname: Belsham
authors.forename: A E
authors.initials: AE
authors.lastname: Willis
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002457:Cell Extracts; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D018387:Codon, Initiator / Q000235:genetics; D004686:Encephalomyocarditis virus / Q000235:genetics; D005796:Genes / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009690:Nucleic Acid Conformation; D009928:Organ Specificity; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism; D012156:Reticulocytes; D012229:Rhinovirus / Q000235:genetics; D012270:Ribosomes / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D002457:Cell Extracts; D018387:Codon, Initiator; D016271:Proto-Oncogene Proteins c-myc; D012315:RNA Caps; D015534:Trans-Activators