Schuler G D, Cole M D
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08540.
Cell. 1988 Dec 23;55(6):1115-22. doi: 10.1016/0092-8674(88)90256-5.
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.
mRNA 周转的调控已成为淋巴细胞因子和癌基因表达中的一个重要控制点。我们研究了一种单核细胞肿瘤，其中 GM-CSF 表达的激活源于正常寿命较短的 GM-CSF mRNA 的组成型稳定化。GM-CSF 基因的种系 3' 非翻译区与新霉素报告基因的连接表明，mRNA 稳定化是由肿瘤特异性反式作用因子介导的，而不是由 GM-CSF 基因本身的改变介导的。值得注意的是，c-myc 和 c-fos 的 3' 非翻译区与新霉素的类似融合产生的 mRNA 在所有细胞（包括肿瘤细胞）中都迅速周转。这些结果表明，富含 AU 的 mRNA 周转信号在同一细胞内被反式差异性识别。
