4.7 Article

Mean-field theory accurately captures the variation of copy number distributions across the mRNA life cycle

Journal

PHYSICAL REVIEW E
Volume 105, Issue 1, Pages -

Publisher

AMER PHYSICAL SOC
DOI: 10.1103/PhysRevE.105.014410

Keywords

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Funding

  1. Leverhulme Trust research award [RPG-2020-327]

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In this study, a stochastic model of gene switching and mRNA life cycle stages is considered. A mean-field approach is constructed to obtain steady-state distributions of transcript molecules at each stage. The results indicate that any bimodality gradually disappears in a population of identical cells as mRNA progresses through its life cycle.
We consider a stochastic model where a gene switches between two states, an mRNA transcript is released in the active state, and subsequently it undergoes an arbitrary number of sequential unimolecular steps before being degraded. The reactions effectively describe various stages of the mRNA life cycle such as initiation, elongation, termination, splicing, export, and degradation. We construct a mean-field approach that leads to closed-form steady-state distributions for the number of transcript molecules at each stage of the mRNA life cycle. By comparison with stochastic simulations, we show that the approximation is highly accurate over all the parameter space, independent of the type of expression (constitutive or bursty) and of the shape of the distribution (unimodal, bimodal, and nearly bimodal). The theory predicts that in a population of identical cells, any bimodality is gradually washed away as the mRNA progresses through its life cycle.

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