Stochastic modeling of the mRNA life process: A generalized master equation

The mRNA life cycle is a complex biochemical process, involving transcription initiation, elongation, termination, splicing, and degradation. Each of these molecular events is multistep and can create a memory. The effect of this molecular memory on gene expression is not clear, although there are many related yet scattered experimental reports. To address this important issue, we develop a general theoretical framework formulated as a master equation in the sense of queue theory, which can reduce to multiple previously studied gene models in limiting cases. This framework allows us to interpret experi-mental observations, extract kinetic parameters from experimental data, and identify how the mRNA kinetics vary under regu-latory influences. Notably, it allows us to evaluate the influences of elongation processes on mature RNA distribution; e.g., we find that the non-exponential elongation time can induce the bimodal mRNA expression and there is an optimal elongation noise intensity such that the mature RNA noise achieves the lowest level. In a word, our framework can not only provide insight into complex mRNA life processes but also bridge a dialogue between theoretical studies and experimental data.

Automated summary

This study develops a general theoretical framework to explain the complex biochemical process of mRNA life cycle and extract kinetic parameters from experimental data. The framework allows evaluation of the influence of elongation processes on mature RNA distribution, and identifies the optimal elongation noise intensity for achieving the lowest mature RNA noise levels.