title: Kinetic analysis of the effects of target structure on siRNA efficiency.
abstract: RNAi efficiency for target cleavage and protein expression is related to the target structure. Considering the RNA-induced silencing complex (RISC) as a multiple turnover enzyme, we investigated the effect of target mRNA structure on siRNA efficiency with kinetic analysis. The 4-step model was used to study the target cleavage kinetic process: hybridization nucleation at an accessible target site, RISC-mRNA hybrid elongation along with mRNA target structure melting, target cleavage, and enzyme reactivation. At this model, the terms accounting for the target accessibility, stability, and the seed and the nucleation site effects are all included. The results are in good agreement with that of experiments which show different arguments about the structure effects on siRNA efficiency. It shows that the siRNA efficiency is influenced by the integrated factors of target's accessibility, stability, and the seed effects. To study the off-target effects, a simple model of one siRNA binding to two mRNA targets was designed. By using this model, the possibility for diminishing the off-target effects by the concentration of siRNA was discussed.
authors.affiliation: Department of Physics, Wuhan University, Wuhan, Hubei 430072, People's Republic of China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Chen
authors.forename: Wenbing
authors.initials: W
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D007700:Kinetics; D008954:Models, Biological; D059367:RNA Cleavage; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex