C-FOS MESSENGER-RNA INSTABILITY DETERMINANTS PRESENT WITHIN BOTH THE CODING AND THE 3'-NON-CODING REGION LINK THE DEGRADATION OF THIS MESSENGER-RNA TO ITS TRANSLATION

The instability of oncogenic mRNA such as c-fos mRNA is controlled in cis by sequences present in both the coding and the 3' untranslated re gions (3'UTR). The latter contains AU-rich elements (ARE) which, depen ding on the cellular context, mediate either their rapid degradation o r inhibit their translation. These observations, along with the known increase of the Life spans of many unstable mRNA promoted by inhibitor s of protein synthesis, raise the possibility that both processes are linked. To investigate further the putative involvement of translation in both coding region and ARE-mediated rapid decay of c-fos mRNA, we designed an expression vector based on the use of the ferritin mRNA ir on regulatory element (IRE). The latter structure links translation to intracellular iron concentration when inserted at the proper location within the 5'UTR. Rapid degradation of a beta-globin/c-fos 3'UTR cons truct was prevented by Desferrioxamine, an iron chelator, and facilita ted by ferric ammonium citrate or hemin, while stability of other mRNA s not containing the IRE or the ARE were unchanged. The same conclusio n was reached when tbe stability of a c-fos mRNA devoid of ARE was ass essed in function of iron availability.