Suppr超能文献

miRNA 介导的负反馈对基因表达噪声的影响。

Effects of microRNA-mediated negative feedback on gene expression noise.

机构信息

Department of Biological Sciences, Indian Institute of Science Education And Research Kolkata Mohanpur, Nadia, West Bengal, India.

Centre for BioSystems Science and Engineering, Indian Institute of Science, Bengaluru, India.

出版信息

Biophys J. 2023 Nov 7;122(21):4220-4240. doi: 10.1016/j.bpj.2023.09.019. Epub 2023 Oct 6.

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally in eukaryotes by binding with target mRNAs and preventing translation. miRNA-mediated feedback motifs are ubiquitous in various genetic networks that control cellular decision making. A key question is how such a feedback mechanism may affect gene expression noise. To answer this, we have developed a mathematical model to study the effects of a miRNA-dependent negative-feedback loop on mean expression and noise in target mRNAs. Combining analytics and simulations, we show the existence of an expression threshold demarcating repressed and expressed regimes in agreement with earlier studies. The steady-state mRNA distributions are bimodal near the threshold, where copy numbers of mRNAs and miRNAs exhibit enhanced anticorrelated fluctuations. Moreover, variation of negative-feedback strength shifts the threshold locations and modulates the noise profiles. Notably, the miRNA-mRNA binding affinity and feedback strength collectively shape the bimodality. We also compare our model with a direct auto-repression motif, where a gene produces its own repressor. Auto-repression fails to produce bimodal mRNA distributions as found in miRNA-based indirect repression, suggesting the crucial role of miRNAs in creating phenotypic diversity. Together, we demonstrate how miRNA-dependent negative feedback modifies the expression threshold and leads to a broader parameter regime of bimodality compared to the no-feedback case.

摘要

微小 RNA(miRNAs)是一种小的非编码 RNA,通过与靶 mRNA 结合并阻止翻译,在真核生物中转录后调节基因表达。miRNA 介导的反馈基序在控制细胞决策的各种遗传网络中普遍存在。一个关键问题是这种反馈机制如何影响基因表达噪声。为了回答这个问题,我们开发了一个数学模型来研究 miRNA 依赖性负反馈回路对靶 mRNA 平均表达和噪声的影响。通过分析和模拟相结合,我们展示了存在一个表达阈值,该阈值与早期研究一致,将受抑制和表达的区域分隔开来。在阈值附近,mRNA 和 miRNA 的拷贝数表现出增强的反相关波动,稳态 mRNA 分布呈双峰模式。此外,负反馈强度的变化会改变阈值位置并调节噪声分布。值得注意的是,miRNA-mRNA 结合亲和力和反馈强度共同塑造了双峰模式。我们还将我们的模型与直接的自动抑制基序进行了比较,其中一个基因产生自己的抑制剂。自动抑制不能像基于 miRNA 的间接抑制那样产生双峰 mRNA 分布,这表明 miRNA 在产生表型多样性方面起着至关重要的作用。总之,我们展示了 miRNA 依赖性负反馈如何改变表达阈值,并导致与无反馈情况相比,双峰性的参数范围更广。

相似文献

1
Effects of microRNA-mediated negative feedback on gene expression noise.
Biophys J. 2023 Nov 7;122(21):4220-4240. doi: 10.1016/j.bpj.2023.09.019. Epub 2023 Oct 6.
2
On the role of extrinsic noise in microRNA-mediated bimodal gene expression.
PLoS Comput Biol. 2018 Apr 17;14(4):e1006063. doi: 10.1371/journal.pcbi.1006063. eCollection 2018 Apr.
3
Quantifying negative feedback regulation by micro-RNAs.
Phys Biol. 2011 Oct;8(5):055002. doi: 10.1088/1478-3975/8/5/055002. Epub 2011 Aug 10.
5
Autoregulation of microRNA biogenesis by let-7 and Argonaute.
Nature. 2012 Jun 28;486(7404):541-4. doi: 10.1038/nature11134.
6
Counter-intuitive stochastic behavior of simple gene circuits with negative feedback.
Biophys J. 2010 May 19;98(9):1742-50. doi: 10.1016/j.bpj.2010.01.018.
9
Negative feedback through mRNA provides the best control of gene-expression noise.
IEEE Trans Nanobioscience. 2011 Sep;10(3):194-200. doi: 10.1109/TNB.2011.2168826.

引用本文的文献

1
Hydrolysis-dependent severing tunes internal monomeric heterogeneity to shape actin length distributions.
bioRxiv. 2025 May 30:2025.05.29.656816. doi: 10.1101/2025.05.29.656816.

本文引用的文献

1
Nonmodular oscillator and switch based on RNA decay drive regeneration of multimodal gene expression.
Nucleic Acids Res. 2022 Apr 22;50(7):3693-3708. doi: 10.1093/nar/gkac217.
3
MomentClosure.jl: automated moment closure approximations in Julia.
Bioinformatics. 2021 Dec 22;38(1):289-290. doi: 10.1093/bioinformatics/btab469.
5
Enhancement of gene expression noise from transcription factor binding to genomic decoy sites.
Sci Rep. 2020 Jun 4;10(1):9126. doi: 10.1038/s41598-020-65750-2.
6
Dynamical phase diagram of an auto-regulating gene in fast switching conditions.
J Chem Phys. 2020 May 7;152(17):174110. doi: 10.1063/5.0007221.
7
Stochastic Modeling of Autoregulatory Genetic Feedback Loops: A Review and Comparative Study.
Biophys J. 2020 Apr 7;118(7):1517-1525. doi: 10.1016/j.bpj.2020.02.016. Epub 2020 Feb 25.
8
Small protein number effects in stochastic models of autoregulated bursty gene expression.
J Chem Phys. 2020 Feb 28;152(8):084115. doi: 10.1063/1.5144578.
9
Single-cell stochastic gene expression kinetics with coupled positive-plus-negative feedback.
Phys Rev E. 2019 Nov;100(5-1):052406. doi: 10.1103/PhysRevE.100.052406.
10
Transient hysteresis and inherent stochasticity in gene regulatory networks.
Nat Commun. 2019 Oct 8;10(1):4581. doi: 10.1038/s41467-019-12344-w.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验