c-myc internal ribosome entry site activity is developmentally controlled and subjected to a strong translational repression in adult transgenic mice

The expression of c-myc proto-oncogene, a key regulator of cell proliferati on and apoptosis, is controlled at different transcriptional and posttransc riptional levels. In particular, the c-myc mRNA contains an internal riboso me entry site (IRES) able to promote translation initiation independently f rom the classical cap-dependent mechanism. We analyzed the variations of c- myc IRES activity ex vivo in different proliferating cell types, and in viv o in transgenic mice expressing a bicistronic dual luciferase construct, c- myc IRES efficiency was compared to that of encephalomyocarditis virus (EMC V) IRES under the same conditions. The c-myc IRES was active but with varia ble efficiency in all transiently transfected cell types; it was also activ e in the 11-day-old (E11) embryo and in some tissues of the E16 embryo. Str ikingly, its activity was undetected or very low in all adult organs tested . In contrast, EMCV IRES was very active in most cell types ex vivo, as wel l as in embryonic and adult tissues. These data suggest a crucial role of I RES in the control of c-myc gene expression throughout development, either during embryogenesis where its activity might participate in cell prolifera tion or later on, where its silencing could contribute to the downregulatio n of c-myc expression, whose deregulation leads to tumor formation.