Contribution of RNA Degradation to Intrinsic and Extrinsic Noise in Gene Expression
Contribution of RNA Degradation to Intrinsic and Extrinsic Noise in Gene Expression
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DOI：
10.1016/j.celrep.2019.03.001
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发表时间：
2019-03-26
期刊：
影响因子：
8.8
通讯作者：
Becskei, Attila
中科院分区：
文献类型：
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作者：
Baudrimont, Antoine;Jaquet, Vincent;Becskei, Attila
基因相同的细胞包含不同数量的分子，即使细胞共享相同的环境。当分子具有低丰度时，这种随机可变性是突出的，这是mRNA噪声的情况。大多数研究集中在转录如何影响mRNA噪音，而对RNA降解的作用知之甚少。为了区分在这些过程中的一对报告mRNA的衰变的波动，我们量化的不相关的内在和相关的外在噪声使用单分子RNA FISH。固有噪声在衰减期间收敛到泊松水平。具有短半衰期的mRNA比稳定的mRNA更容易受到外部噪声的影响。然而，发现快速降解mRNA的Xrn1核酸外切酶和NMD途径具有较低的波动，这减轻了短寿命mRNA的噪声。这允许在mRNA半衰期的整个范围内的低变异性。
Genetically identical cells contain variable numbers of molecules, even if the cells share the same environment. This stochastic variability is prominent when molecules have low abundance, which is the case for mRNA noise. Most studies focused on how transcription affects mRNA noise, and little is known about the role of RNA degradation. To discriminate the fluctuations in these processes during the decay of a pair of reporter mRNAs, we quantified the uncorrelated intrinsic and the correlated extrinsic noise using single-molecule RNA FISH. Intrinsic noise converges to the Poisson level during the decay. mRNAs that have a short half-life are more susceptible to extrinsic noise than stable mRNAs. However, the Xrn1 exonuclease and the NMD pathways, which degrade mRNAs rapidly, were found to have lower fluctuation, which mitigates the noise of the short-lived mRNAs. This permits low variability across the entire range of mRNA half-lives.