Major role for mRNA stability in shaping the kinetics of gene induction.
Major role for mRNA stability in shaping the kinetics of gene induction.
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DOI：
10.1186/1471-2164-11-259
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发表时间：
2010-04-21
期刊：
影响因子：
4.4
通讯作者：
Agami R
中科院分区：
文献类型：
--
作者：
Elkon R;Zlotorynski E;Zeller KI;Agami R
细胞中的mRNA水平由RNA产生和降解的相对速率决定。然而，迄今为止，大多数基因表达谱的分析都集中在调节转录的机制，而mRNA稳定性在调节转录网络的作用在很大程度上被忽视。特别是，转录反应中的动力学波通常被解释为由转录因子的顺序激活引起的。在这项研究中，我们在全球范围内研究了mRNA稳定性在塑造基因反应动力学中的作用。通过分析大量的表达数据集，我们发现诱导速度和mRNA稳定性之间存在显著的全局反相关性，符合动力学数学模型的预测。相反，当分析基因抑制时，动力学和稳定性之间的关系不太显著。通常，在标准条件下稳定的mRNA在刺激后非常迅速地下调。这种效应甚至不能通过转录的完全关闭来解释，因此表明RNA稳定性的强烈调节。总之，我们的研究结果表明，在确定哺乳动物转录网络的诱导动力学的mRNA稳定性的关键作用。
mRNA levels in cells are determined by the relative rates of RNA production and degradation. Yet, to date, most analyses of gene expression profiles were focused on mechanisms which regulate transcription, while the role of mRNA stability in modulating transcriptional networks was to a large extent overlooked. In particular, kinetic waves in transcriptional responses are usually interpreted as resulting from sequential activation of transcription factors. In this study, we examined on a global scale the role of mRNA stability in shaping the kinetics of gene response. Analyzing numerous expression datasets we revealed a striking global anti-correlation between rapidity of induction and mRNA stability, fitting the prediction of a kinetic mathematical model. In contrast, the relationship between kinetics and stability was less significant when gene suppression was analyzed. Frequently, mRNAs that are stable under standard conditions were very rapidly down-regulated following stimulation. Such effect cannot be explained even by a complete shut-off of transcription, and therefore indicates intense modulation of RNA stability. Taken together, our results demonstrate the key role of mRNA stability in determining induction kinetics in mammalian transcriptional networks.
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