Complex degradation processes lead to non-exponential decay patterns and age-dependent decay rates of messenger RNA.
Complex degradation processes lead to non-exponential decay patterns and age-dependent decay rates of messenger RNA.
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DOI：
10.1371/journal.pone.0055442
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Valleriani A
中科院分区：
文献类型：
--
作者：
Deneke C;Lipowsky R;Valleriani A
对mRNA稳定性的实验研究已经建立了活细胞内mRNA量的几种定性不同的衰减模式。此外，已经鉴定了用于mRNA降解的多种不同且复杂的生化途径。本文的主要目的是将有关衰减模式的实验证据和有关mRNA降解多步骤性质的生物化学知识结合在一个连贯的数学理论中。我们首先介绍了mRNA衰变模式和单个mRNA分子的寿命分布之间的数学关系。这种关系表明，在稳态表达水平的mRNA衰减模式必须遵守一个一般的凸性条件，适用于任何降解机制。接下来，我们开发了一个理论，制定为马尔可夫链模型，概括了mRNA降解的多步骤性质的一些方面。我们将我们的理论应用于酵母的实验数据，并明确推导出相应mRNA的寿命分布。因此，我们展示了如何提取mRNA的单分子特性，例如年龄依赖性衰减率和剩余寿命。最后，我们分析了整个translatome的酵母细胞的衰变模式，并表明酵母mRNA可以分为三大类，表现出三种不同的衰变模式。本文提供了一种准确分析非指数mRNA衰减模式的方法和一种使用衰减数据验证不同降解模型的工具。
Experimental studies on mRNA stability have established several, qualitatively distinct decay patterns for the amount of mRNA within the living cell. Furthermore, a variety of different and complex biochemical pathways for mRNA degradation have been identified. The central aim of this paper is to bring together both the experimental evidence about the decay patterns and the biochemical knowledge about the multi-step nature of mRNA degradation in a coherent mathematical theory. We first introduce a mathematical relationship between the mRNA decay pattern and the lifetime distribution of individual mRNA molecules. This relationship reveals that the mRNA decay patterns at steady state expression level must obey a general convexity condition, which applies to any degradation mechanism. Next, we develop a theory, formulated as a Markov chain model, that recapitulates some aspects of the multi-step nature of mRNA degradation. We apply our theory to experimental data for yeast and explicitly derive the lifetime distribution of the corresponding mRNAs. Thereby, we show how to extract single-molecule properties of an mRNA, such as the age-dependent decay rate and the residual lifetime. Finally, we analyze the decay patterns of the whole translatome of yeast cells and show that yeast mRNAs can be grouped into three broad classes that exhibit three distinct decay patterns. This paper provides both a method to accurately analyze non-exponential mRNA decay patterns and a tool to validate different models of degradation using decay data.
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作者：
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影响因子：
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作者：
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作者：
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通讯作者：
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作者：
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