An in-silico human cell model reveals the influence of spatial organization on RNA splicing
Fig 4
Splicing efficiency increases in the presence of speckles in the cells: A) The higher the probability for the splicing particles to transition from the cell nucleus to the speckles, relative to the reverse transition, the higher the localization of splicing particles in speckles. Schematically, the randomly distributed splicing particles (yellow dots) in the cell nucleus (colored in purple), localize in nucleus speckles (blue shaded regions) as the probability imbalance increases (the splicing particles concentration is 1 nM). B) As the percentage of splicing particles located in speckles increases, the number of spliced mRNA also increases. C) This enhancement in mRNA production is highly sensitive to the localization of splicing particles in speckles; with only a 10% localization of splicing particles in speckles, the splicing reaction is enhanced ∼ 250-fold relative to the case with no speckles. D) Noise estimated as coefficient of variation (CV), decreases as a greater percentage of splicing particles are localized in speckles. Splicing particle concentration affects the functional advantage of speckles: E) Enhancement in mRNA production due to the presence of speckles, depends on the U1 splicing particle concentration; F) Effect of the U1 splicing particle concentration on the mRNA production noise. Note that for cells with 0.1 nM U1, below 25% splicing particle localization, the CV is not defined due to lack of mRNA production. For each condition, 20 simulation replicates were performed. For simulation details see Methods.