Bokes Pavol, Hojcka Michal, Singh Abhyudai
IEEE/ACM Trans Comput Biol Bioinform. 2021 Jan-Feb;18(1):272-282. doi: 10.1109/TCBB.2019.2938502. Epub 2021 Feb 3.
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.
内在噪声产生于低拷贝数基因表达过程中，可通过多种调控基序（包括前馈环）进行控制。在此，我们研究一个基于信使核糖核酸（mRNA）分子与由同一基因编码的拮抗微小核糖核酸（miRNA）分子之间相互作用的前馈控制系统实例，旨在量化分子拷贝数的变异性（即噪声）。运用线性噪声近似方法，我们表明，在非爆发性转录情况下，mRNA噪声呈亚泊松分布，并且对物种自然寿命比以及拮抗相互作用强度均呈现非单调响应。此外，我们运用化学反应网络理论证明，在不存在自发mRNA衰变通道的情况下，mRNA拷贝数分布呈泊松分布。在转录爆发的情况下，我们表明前馈控制能够减弱由爆发导致的超泊松基因表达噪声，并且这种效应在蛋白质水平比在mRNA水平更为显著。我们的结果表明，mRNA与miRNA在爆发化学计量以及产生事件时间方面的强耦合，使得基于miRNA的前馈基序成为控制基因表达噪声的一种有效机制。
