Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to Polysomes
Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to Polysomes
复制标题
DOI：
10.1016/s1097-2765(03)00395-2
复制
发表时间：
2003-10-01
期刊：
影响因子：
16
通讯作者：
Holland, EC
中科院分区：
文献类型：
--
作者：
Rajasekhar, VK;Viale, A;Holland, EC
为了确定致癌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信号传导阻断对转录的直接影响相对温和;然而，与多聚核糖体相关的mRNA谱发生了实质性改变。这些观察结果表明，Ras和Akt信号传导的直接作用调节特定mRNA向核糖体的募集，其程度远远大于它们通过转录作用调节mRNA的产生。受影响最大的mRNA是那些编码调节生长、转录调节、细胞与细胞相互作用和形态的蛋白质的mRNA。这些数据支持Ras和Akt信号传导主要通过改变转录组并产生与主动翻译多核糖体相关的mRNA组成的根本转变来导致细胞转化的模型。
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.