Analysis of the c-myc IRES; a potential role for cell-type specific trans-acting factors and the nuclear compartment

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 mechani sm of internal ribosome entry. However, there is also some evidence suggest ing that c-myc mRNA translation can occur via the conventional cap-dependen t scanning mechanism. Using both bicistronic and monocistronic mRNAs contai ning the c-myc 5' UTR, we demonstrate that both mechanisms can contribute t o c-myc protein synthesis. A wide range of cell types are capable of initia ting 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 cellu lar concentration of non-canonical translation factors. Interestingly, the c-myc IRES is 7-fold more active than the human rhinovirus 2 (HRV2) IRES an d 5-fold more active than the encephalomyocarditis virus (EMCV) IRES, Howev er, the protein requirements for the c-myc IRES must differ significantly f rom these viral IRESs, since an unidentified nuclear event appears to be a pre-requisite for efficient c-myc IRES-driven initiation.