Rajasekhar Vinagolu K, Viale Agnes, Socci Nicholas D, Wiedmann Martin, Hu Xiaoyi, Holland Eric C
Department of Surgery (Neurosurgery), Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Mol Cell. 2003 Oct;12(4):889-901. doi: 10.1016/s1097-2765(03)00395-2.
In order to determine the global effects of oncogenic Ras and Akt signaling pathways on translational efficiencies, we compared the gene expression profiles of total cellular mRNA and mRNA associated with polysomes. We found that the immediate effect of Ras and Akt signaling blockade on transcription was relatively modest; however, the profile of mRNA associated with polysomes was substantially altered. These observations indicate that the immediate effect of Ras and Akt signaling regulates the recruitment of specific mRNAs to ribosomes to a far greater extent than they regulate the production of mRNAs by transcriptional effects. The mRNAs most affected are those encoding proteins that regulate growth, transcription regulation, cell to cell interactions, and morphology. These data support a model whereby Ras and Akt signaling primarily lead to cellular transformation by altering the transcriptome and producing a radical shift in the composition of mRNAs associated with actively translating polysomes.
为了确定致癌性Ras和Akt信号通路对翻译效率的整体影响，我们比较了总细胞mRNA和与多核糖体相关的mRNA的基因表达谱。我们发现，Ras和Akt信号通路阻断对转录的直接影响相对较小；然而，与多核糖体相关的mRNA谱发生了显著改变。这些观察结果表明，Ras和Akt信号通路的直接作用在更大程度上调节特定mRNA与核糖体的结合，而不是通过转录作用调节mRNA的产生。受影响最大的mRNA是那些编码调节生长、转录调控、细胞间相互作用和形态的蛋白质的mRNA。这些数据支持了一个模型，即Ras和Akt信号通路主要通过改变转录组并在与活跃翻译的多核糖体相关的mRNA组成上产生根本性转变来导致细胞转化。
