Research On The Kinetics Of RNA Silencing Pathway

As a new discovered gene regulation mechanism, RNA silencing pathway exists in a wide variety of eukaryotic organisms. There are diverse patterns of RNA silencing pathway which regulates various developmental and physiological processes such as maintaining the genome stability, developmental timing, virus defense and so on. Meanwhile, as an efficient experimental tool for gene function, RNA silencing has enormous potentiality in the field of functional genomics, gene therapy, drug development and so on. Researching on the dynamic mechanism of RNA silencing pathway is helpful to understand the impacts of parameters and processes on the effect and duration of gene silencing and plan and monitor the real experiments.Several mathematical models have been proposed to explain the experimental phenomena of RNA silencing. Although these models are relatively successful, they have limitations. Some hypothesis of processes involved in RNA silencing pathway of these models are in conflict with new experimental observations. Based on the latest experimental results and theoretical research, we investigate the kinetic behavior of the core pathway of RNA silencing and plant posttranscriptional gene silencing in single cell level.Firstly, simplified mathematical models of the core pathway of RNA silencing pathway in which RNA mediates mRNAs cleavage and translation repression is proposed. It is found that the stability of sRNAs impacts on the duration of gene silencing and the rate of the banding of siRNAs to mRNAs impacts on the effect of gene silencing. The siRNAs dosage needed in the RNA silencing pathway in which sRNAs mediate translation repression must be in the same order of magnitude with mRNAs concentration.Secondly, basic mathematical model of plant posttranscriptional gene silencing pathway is proposed, the dynamics of it is analysised, it cannot explain transgene induced silencing. So two extensions are added to the basic model, primed amplification of garbage RNA pieces and unprimed amplification by a sigmoid amplification. The extended models provide explanations for dose dependent dsRNA induced silencing, transgene induced silencing and stability against self-directed response. When the number of transgene copies is within certain value range, the concentration of mRNA oscillates because of the existence of RNA silencing.