The effect of microRNA on protein variability and gene expression fidelity

Small regulatory RNA molecules such as microRNA modulate gene expression through inhibiting the translation of messenger RNA (mRNA). Such posttranscriptional regulation has been recently hypothesized to reduce the stochastic vari-ability of gene expression around average levels. Here, we quantify noise in stochastic gene expression models with and without such regulation. Our results suggest that silencing mRNA posttranscriptionally will always increase, rather than decrease, gene expression noise when the silencing of mRNA also increases its degradation, as is expected for microRNA interactions with mRNA. In that regime, we also find that silencing mRNA generally reduces the fidelity of signal transmission from determinis-tically varying upstream factors to protein levels. These findings suggest that microRNA binding to mRNA does not generically confer precision to protein expression.