Nucleic Acids Research, 2000, Vol. 28, No. 3 687-694
© 2000 Oxford University Press
Analysis of the c-myc IRES; a potential role for cell-type specific trans-acting factors and the nuclear compartment
Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK
The 5' UTR of c-myc mRNA contains an internal ribosome 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.
* To whom correspondence should be addressed. Tel: +44 116 2523363; Fax: +44 116 2523369; Email: aew5@le.ac.uk Present addresses: Mark Stoneley, Department of Biochemistry and Molecular Biology, The University of Leeds, Leeds LS2 9JT, UK Graham J. Belsham, BBSRC, Institute for Animal Health, Pirbright, Woking GU4 0NF, UK
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