Petri Net Modelling Validates RNAi-mediated Gene Silencing in Suppressing the Disease Apolipoprotein B

Abstract

RNA interference, also known as RNAi, RNA silencing, or posttranscriptional gene silencing (PTGS), is a mechanism present in almost all eukaryotes, which functions like an intracellular immune system.The phenomenon of RNA interference takes place between the transcription of DNA and the translation to proteins. In this study, we first presented a model of the RNA silencing mechanism. The model was constructed based on four important factors: stochastic translocation of mRNA, stochastic dsRNA synthesis,formation of RISC protein, and a random supply of primed as well as unprimed dsRNA. We then applied our model to a primate-specific model for the purpose of validating and predicting the apolipoprotein B (APOB)mRNA suppression in a cynomolgus monkey's liver. The simulation results of our model were strongly consistent with known biological phenomena. To our knowledge, this is the first time that hybrid functional Petri net (HFPN) was used to construct a mammal-specific model which was capable of validating and predicting the suppression of APOB mRNA in non-human primates.