title: Non-Catalytic RISCs and Kinetics Determine Mammalian siRNA Sub-Cellular Localization.
abstract: Small interfering RNAs (siRNAs) are fundamental to the regulation of cell function. Much is known about its gene interfering mechanism, but a kinetic description of it is still lacking. Here, we derived a set of reaction-diffusion equations for multiple RNA-induced silencing complex (RISC) pathways that give quantitative temporal and spatial descriptions of the siRNA process in mammalian cell, and are able to correctly describe all salient experimentally observed patterns of sub-cellular siRNA localization, including those that, at first glance, appear irreconcilable. These results suggest siRNA sub-cellular localization mainly concerns the non-catalytic RISC-target complex, and is caused by the selectiveness of RISC-target interaction and the permeability of the nuclear membrane to siRNA strands but not to RISC-target complexes. Our method is expected to be useful in devising RNAi based cell regulation strategies.
authors.affiliation: Institute of Biological Sciences and Biotechnology, Beijing Jiaotong University, Beijing 100044, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Ji
authors.affiliation: Department of Chemistry, Beijing Jiaotong University, Beijing 100044, China.
authors.forename: Lianyun
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Biomedical Sciences and Engineering, National Central University, Zhongli District, Taoyuan City 32001, Taiwan.
authors.forename: Ya-Hsin
authors.initials: YH
authors.lastname: Tien
authors.affiliation: Department of Biomedical Sciences and Engineering, National Central University, Zhongli District, Taoyuan City 32001, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Peng
authors.affiliation: Department of Biomedical Sciences and Engineering, National Central University, Zhongli District, Taoyuan City 32001, Taiwan.|Department of Physics, Chung Yuan Christian University, Zhongli District, Taoyuan City 32023, Taiwan.|Center for Dynamical Biomarkers and Translational Medicine, National Central University, Zhongli District, Taoyuan City 32001, Taiwan.
authors.forename: Hoong-Chien
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000818:Animals; D001692:Biological Transport; D007700:Kinetics; D008322:Mammals / Q000235:genetics*; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000032:analysis* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex