Abstract
Spatial organization is a fundamental characteristic of cells, achieved by utilizing both membrane-bound and non-bound organelles. We construct a spatially resolved human whole-cell (HeLa) model from experiment-based structural, morphological and reaction network data to describe the mRNA splicing process and dynamics of splicing particles. We performed stochastic simulations for up to 15 minutes of biological time of the entire cell. We find that the number of nuclear pore complexes controls the number of assembled splicing particles; that even a slight increase of splicing particle localization in nuclear speckles (non-membrane-bound organelles) leads to a disproportionate enhancement of mRNA splicing and reduction in the transcript noise; and that compartmentalization is critical for the yield of correctly assembled splicing particles. Our model also predicts that the distance between genes and speckles has a considerable effect on the mRNA production rate, further emphasizing the importance of genome organization around speckles. The HeLa cell model, including organelles and subcompartments, provides an adaptable foundation to study many cellular processes which are strongly modulated by spatio-temporal heterogeneity.
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