Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Nat Genet. 2011 Aug 21;43(9):854-9. doi: 10.1038/ng.905.
MicroRNAs (miRNAs) are short, highly conserved noncoding 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 although 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 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 show that miRNAs can act both as a switch and as a fine-tuner of gene expression.
微 RNA(miRNA)是短的、高度保守的非编码 RNA 分子,以序列依赖性方式抑制基因表达。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 调节的情况下靶基因的蛋白质表达。我们发现,尽管平均抑制水平适中,与以前的基于群体的测量结果一致,但单个细胞之间的抑制差异很大。特别是,我们表明 miRNA 的调节建立了一个靶 mRNA 的阈值水平,低于该水平蛋白质的产生受到高度抑制。在这个阈值附近,蛋白质表达对靶 mRNA 的输入反应灵敏,与分子滴定的数学模型一致。这些结果表明,miRNA 可以作为基因表达的开关和微调器发挥作用。