Single‐cell mRNA profiling reveals the hierarchical response of mi RNA targets to mi RNA induction

mi RNA s are small RNA s that regulate gene expression post‐transcriptionally. By repressing the translation and promoting the degradation of target mRNA s, mi RNA s may reduce the cell‐to‐cell variability in protein expression, induce correlations between target expression levels, and provide a layer through which targets can influence each other's expression as “competing RNA s” (ce RNA s). However, experimental evidence for these behaviors is limited. Combining mathematical modeling with RNA sequencing of individual human embryonic kidney cells in which the expression of two distinct mi RNA s was induced over a wide range, we have inferred parameters describing the response of hundreds of mi RNA targets to mi RNA induction. Individual targets have widely different response dynamics, and only a small proportion of predicted targets exhibit high sensitivity to mi RNA induction. Our data reveal for the first time the response parameters of the entire network of endogenous mi RNA targets to mi RNA induction, demonstrating that mi RNA s correlate target expression and at the same time increase the variability in expression of individual targets across cells. The approach is generalizable to other mi RNA s and post‐transcriptional regulators to improve the understanding of gene expression dynamics in individual cell types.