Stochastic Transcription Elongation via Rule Based Modelling

Transcription elongation is the mechanism by which RNA polymerase (RNAP) moves along template unzipped DNA and synthesizes a complementary single-stranded RNA. During the elongation, RNAP forms a stable transcription elongation complex (TEC) with the template DNA and the nascent RNA. The mechanism involves back-tracked and forward-tracked modes of TEC and the polymerisation and depolymerisation of RNA. To capture the stochasticity of the elongation, we describe the mechanism in terms of rule-based modelling through the TEC’s local window frame of adjacent active sites. In this way, we can uniformly derive the variations of known kinetic pathways for various interaction combinations of TEC’s active sites. From the compact interactions at local sites, we find abstracted rules for the elongation. As the semantic counterpart, we derive quasi-steady state approximations to the chemical master equations. The stochastic models are thermodynamically interpreted as the free energy distributions of agents with variant configurations.