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MicroRNAs dampen noisy expression

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MicroRNAs repress gene expression by triggering mRNA degradation and inhibiting translation, but they generally have very modest effects on individual target genes. Now, Alexander van Oudenaarden and colleagues explore a possible function for microRNAs in the repression of expression noise (Science 348, 128–132, 2015). The authors used mouse embryonic stem cells to quantify the effect of endogenous microRNAs on the levels of fluorescent reporter proteins in single cells and used this system to measure noise in protein expression when they varied the numbers and strengths of microRNA-binding sites in the reporter genes. They observed that microRNAs caused a reduction in noise at low levels of reporter protein expression and an increase in noise at high levels of reporter expression. They used the data to construct a mathematical model of microRNA-regulated gene expression noise. The model and the experiments suggest that reduction of intrinsic transcriptional noise is a general property of microRNAs. The authors also show that combinatorial microRNA regulation, in which mRNAs contain many binding sites for different microRNAs, enhances noise reduction. The authors conclude that the function of microRNAs in noise reduction may explain both combinatorial microRNA targeting and preferential targeting of weakly expressed genes by microRNAs.

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Niemitz, E. MicroRNAs dampen noisy expression. Nat Genet 47, 429 (2015). https://doi.org/10.1038/ng.3296

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