GM-CSF and oncogene mRNA stabilities are independently regulated in trans in a mouse monocytic tumor

Regulation of mRNA turnover has emerged as an important control point in lymphokine and oncogene expression. We have studied a monocytic tumor in which activation of GM-CSF expression results from the constitutive stabilization of the normally short-lived GM-CSF mRNA. Linkage of the germ-line 3' untranslated region of the GM-CSF gene to a neo reporter gene demonstrated that mRNA stabilization is mediated by a tumor-specific trans-acting factor(s), rather than by an alteration of the GM-CSF gene itself. Significantly, similar fusions of the c-myc and c-fos 3' untranslated regions to neo yielded mRNAs that turned over rapidly in all cells, including the tumor cells. These results demonstrate that AU-rich mRNA turnover signals are recognized differentially in trans within the same cell.