mRNA Turnover Rate Limits siRNA and microRNA Efficacy

Based on a simple model of the mRNA life cycle, we predict that mRNAs with high turnover rates in the cell are more difficult to perturb with RNAi. We test this hypothesis using a luciferase reporter system and obtain additional evidence from a variety of large-scale data sets, including microRNA overexpression experiments and RT–qPCR-based efficacy measurements for thousands of siRNAs. Our results suggest that mRNA half-lives will influence how mRNAs are differentially perturbed whenever small RNA levels change in the cell, not only after transfection but also during differentiation, pathogenesis and normal cell physiology