An agent-based model for mRNA export through the nuclear pore complex.
Bottom Line: On running the model, we observed that mRNA export is sensitive to the number and distribution of transport receptors coating the mRNA and that there is a rate-limiting step in the nuclear basket that is potentially associated with the mRNA reconfiguring itself to thread into the central channel.Of note, our results also suggest that using a single location-monitoring mRNA label may be insufficient to correctly capture the time regime of mRNA threading through the pore and subsequent transport.This has implications for future experimental design to study mRNA transport dynamics.
Affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, Graduate Program in Chemical Biology, Berkeley, Berkeley, CA 94720.Show MeSH
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Mentions: We developed a three-dimensional (3D), computationally efficient, and spatiotemporally detailed agent-based model (ABM) to simulate molecular diffusion, binding, and unbinding events with consideration for physical factors such as molecular crowding and steric repulsion (Azimi et al., 2011; Azimi and Mofrad, 2013). We performed in silico experiments to determine the ability of our ABM model to recapitulate experimentally determined, size-dependent permeabilities for passive cargoes as well as for Impβ (Riddick and Macara, 2005; Mohr et al., 2009). After the microinjection of noninteracting species agents in the cytoplasm, the NPC was observed to inhibit the influx of larger species while allowing smaller species to diffuse through the pore (Figure 1). Influx rates of noninteracting species with Stokes radii of ∼1 nm are on the order of 0.1 s−1, whereas larger species with Stokes radii of >2.5 nm have influx rates of <0.001 s−1. As expected, a reduced influx rate was not observed for larger species that had affinity for the FG Nups. To test this behavior, we repeated experiments similar to those performed for noninteracting species, replacing the noninteracting species with 2.5 μM labeled Impβ in addition to the steady-state concentration of unlabeled Impβ (unpublished data). The influx rate of Impβ into the nucleus was observed to be 0.367 s−1. This value is comparable with an experimentally measured influx rate of 0.4 s−1 for Impβ (Riddick and Macara, 2005).
Affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, Graduate Program in Chemical Biology, Berkeley, Berkeley, CA 94720.