MicroRNAs can generate thresholds in target gene expression.

MicroRNAs can generate thresholds in target gene expression.
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DOI:
10.1038/ng.905
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发表时间:
2011-08-21
期刊:
影响因子:
30.8
通讯作者:
van Oudenaarden, Alexander
van Oudenaarden, Alexander
中科院分区:
生物学1区
文献类型:
--
作者:
Mukherji, Shankar;Ebert, Margaret S.;Zheng, Grace X. Y.;Tsang, John S.;Sharp, Phillip A.;van Oudenaarden, Alexander

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MicroRNAs(MiRNAs)是一种短的、高度保守的非编码RNA分子,以序列依赖的方式抑制基因表达。我们使用定量荧光显微镜和流式细胞术进行单细胞测量,以监测在存在和不存在miRNA调控的情况下目标基因的蛋白表达。我们发现,虽然抑制的平均水平是适度的,与之前基于群体的测量结果一致,但单个细胞之间的抑制程度差异很大。特别是,我们证明了miRNAs的调节建立了一个靶向信使RNA(MRNA)的阈值水平,低于这个阈值水平,蛋白质生产被高度抑制。在这个阈值附近,蛋白质表达对目标mRNA的输入敏感,这与分子滴定的数学模型一致。这些结果表明,miRNAs既可以作为基因表达的开关,也可以作为微调因子。
MicroRNAs (miRNAs) are short, highly conserved non-coding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene’s protein expression in the presence and absence of regulation by miRNA. We find that while the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target messenger RNA (mRNA) below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results demonstrate that miRNAs can act both as a switch and as a fine-tuner of gene expression.
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