Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress.
Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress.
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DOI：
10.15252/msb.20156423
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发表时间：
2016-01-20
影响因子：
9.9
通讯作者：
Vogel C
中科院分区：
文献类型：
--
作者：
Cheng Z;Teo G;Krueger S;Rock TM;Koh HW;Choi H;Vogel C
mRNA与蛋白质水平调控的相对重要性仍在争论中。为了在动态系统中解决这个问题，我们绘制了哺乳动物细胞对二硫苏糖醇诱导的30 h应激反应的蛋白质组学和转录组学变化。具体而言，我们估计了RNA和蛋白质合成和降解的动力学参数，并使用新的统计工具将响应模式解卷积为每个监管水平的共同和独特。总体而言，两个监管水平同样重要，但对分子浓度的影响不同。mRNA和蛋白质的变化在2 - 8小时之间达到峰值，但mRNA表达倍数的变化远小于蛋白质的变化。mRNA浓度以短暂的脉冲状模式变化，并在实验结束时恢复到接近处理前水平的值。与此相反，蛋白质浓度切换只有一次，并建立了一个新的稳定状态，与蛋白质调控的主导作用，在错误折叠应力一致。最后，我们产生了一些基因的特定调控模式的假设。
The relative importance of regulation at the mRNA versus protein level is subject to ongoing debate. To address this question in a dynamic system, we mapped proteomic and transcriptomic changes in mammalian cells responding to stress induced by dithiothreitol over 30 h. Specifically, we estimated the kinetic parameters for the synthesis and degradation of RNA and proteins, and deconvoluted the response patterns into common and unique to each regulatory level using a new statistical tool. Overall, the two regulatory levels were equally important, but differed in their impact on molecule concentrations. Both mRNA and protein changes peaked between two and eight hours, but mRNA expression fold changes were much smaller than those of the proteins. mRNA concentrations shifted in a transient, pulse‐like pattern and returned to values close to pre‐treatment levels by the end of the experiment. In contrast, protein concentrations switched only once and established a new steady state, consistent with the dominant role of protein regulation during misfolding stress. Finally, we generated hypotheses on specific regulatory modes for some genes.