MicroRNA Based Feedforward Control of Intrinsic Gene Expression Noise
MicroRNA Based Feedforward Control of Intrinsic Gene Expression Noise
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DOI：
10.1109/tcbb.2019.2938502
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发表时间：
2021-01-01
影响因子：
4.5
通讯作者：
Singh, Abhyudai
中科院分区：
文献类型：
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作者：
Bokes, Pavol;Hojcka, Michal;Singh, Abhyudai
在低拷贝数的基因表达中产生的内在噪声可以由多种调控基序控制，包括前馈回路。在这里，我们研究了一个前馈控制系统的例子，该系统基于mRNA分子与由同一基因编码的拮抗microRNA分子之间的相互作用，旨在量化分子拷贝数的可变性（或噪声）。利用线性噪声近似，我们发现在非突发转录的情况下，mRNA噪声是亚泊松的，并且对物种自然寿命比和拮抗相互作用的强度都表现出非单调的响应。此外，我们使用化学反应网络理论证明了在没有自发的mRNA衰变通道的情况下，mRNA拷贝数分布是泊松的。在转录爆发的情况下，我们发现前馈控制可以减弱由爆发引起的超泊松基因表达噪声，并且在蛋白质水平上的效果比在mRNA水平上的效果更可观。我们的研究结果表明，mRNA和microRNA在突发化学计量和生产事件时间上的强耦合使得基于microRNA的前馈基序成为控制基因表达噪声的有效机制。
Intrinsic noise, which arises in gene expression at low copy numbers, can be controlled by diverse regulatory motifs, including feedforward loops. Here, we study an example of a feedforward control system based on the interaction between an mRNA molecule and an antagonistic microRNA molecule encoded by the same gene, aiming to quantify the variability (or noise) in molecular copy numbers. Using linear noise approximation, we show that the mRNA noise is sub-Poissonian in case of non-bursty transcription, and exhibits a nonmonotonic response both to the species natural lifetime ratio and to the strength of the antagonistic interaction. Additionally, we use the Chemical Reaction Network Theory to prove that the mRNA copy number distribution is Poissonian in the absence of spontaneous mRNA decay channel. In case of transcriptional bursts, we show that feedforward control can attenuate the super-Poissonian gene-expression noise that is due to bursting, and that the effect is more considerable at the protein than at the mRNA level. Our results indicate that the strong coupling between mRNA and microRNA in the sense of burst stoichiometry and also of timing of production events renders the microRNA based feedforward motif an effective mechanism for the control of gene expression noise.