Enhancement of protein productivity of cell by stabilizing mRNA

一个结构化的模型预测，mRNA的稳定结合抑制细胞生长可以提高哺乳动物细胞的蛋白质产量。我们用实验方法证实了这一预测。以mRNA稳定的抗体为例，证实mRNA在细胞内的积累和每细胞的蛋白产量随着细胞生长速度的降低而增加。在培养基中添加咖啡因或白细胞介素6是抑制细胞生长速度以提高蛋白质产量的最佳方法。我们试图通过删除3'非翻译区富含AU的区域来稳定小鼠白细胞介素2的mRNA，这是不稳定mRNA的一个例子。转染了修饰mRNA的小鼠骨髓瘤细胞产生了大量的白细胞介素。

A structured model predicts that stabilization of mRNA combined with suppression of cell growth enhances the protein production rate of mammalian cells. We confirmed this prediction experimentally as follows.1. Choosing antibody as an example of ehich the mRNA was stable we confirmed that the mRNA accumulated in cells and the protein production rate per cell increased at the same time as the growth rate of the cells decreased.3. Addition of caffeine or interleukin 6 into culture medium was the best method to suppress cell growth rate for enhancing the protein productivity.2. We tried to stabilize mRNA of mouse interleukin 2 which is an example of unstable mRNAs by deleting AU rich region at the 3' untranslated region. Mouse myeloma cells transfected with the modified mRNA produced enhanced amount of the interleukin.