Larsson, ErikSander, ChrisMarks, Debora2011-04-112010Larsson, Erik, Chris Sander, and Debora Marks. 2010. mRNA turnover rate limits siRNA and microRNA efficacy. Molecular Systems Biology 6: 433.1744-4292http://nrs.harvard.edu/urn-3:HUL.InstRepos:4820784Based 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.en-USmicroRNAmRNA decayRNAisiRNAJournal Article2011-04-1110.1038/msb.2010.89