Modeling recursive RNA interference.
An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments.
Marshall
Wallace F
WF
Department of Biochemistry and Biophysics, Integrative Program in Quantitative Biology, University of California San Francisco, San Francisco, California, United States of America. wmarshall@biochem.ucsf.edu
D019295:Computational Biology; D017930:Genes, Reporter; D005821:Genetic Techniques; D008957:Models, Genetic; D021141:Nucleic Acid Amplification Techniques; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics; D014162:Transfection
D034741:RNA, Small Interfering; D012324:RNA-Dependent RNA Polymerase; D043244:Ribonuclease III