MicroRNA control of protein expression noise

作者：Jörn M. Schmiedel, Sandy Klemm, Yannan Zheng, Apratim Sahay, Nils Blüthgen, Debora S. Marks, Alexander van Oudenaarden · 发表于：Science · 年份：2015 · DOI：10.1126/science.aaa1738 · 被引用次数：421 · 研究领域：MicroRNA in disease regulation、RNA Research and Splicing、Gene Regulatory Network Analysis

MicroRNAs (miRNAs) repress the expression of many genes in metazoans by accelerating messenger RNA degradation and inhibiting translation, thereby reducing the level of protein. However, miRNAs only slightly reduce the mean expression of most targeted proteins, leading to speculation about their role in the variability, or noise, of protein expression. We used mathematical modeling and single-cell reporter assays to show that miRNAs, in conjunction with increased transcription, decrease protein expression noise for lowly expressed genes but increase noise for highly expressed genes. Genes that are regulated by multiple miRNAs show more-pronounced noise reduction. We estimate that hundreds of (lowly expressed) genes in mouse embryonic stem cells have reduced noise due to substantial miRNA regulation. Our findings suggest that miRNAs confer precision to protein expression and thus offer plausible explanations for the commonly observed combinatorial targeting of endogenous genes by multiple miRNAs, as well as the preferential targeting of lowly expressed genes.