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An agent-based model for mRNA export through the nuclear pore complex.

Azimi M, Bulat E, Weis K, Mofrad MR - Mol. Biol. Cell (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, Graduate Program in Chemical Biology, Berkeley, Berkeley, CA 94720.

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A cartoon representation of the NPC's environment (not to scale) projected onto a two-dimensional, on-lattice ABM with agents (spheres) representing protein factors. These agents move within the system and interact with other agents within their von Neumann neighborhood. One such neighborhood of cells is highlighted in gray for the smaller green agent that is pointed to by an arrow. The actual model consists of a 3D representation of the NPC structure and physiologically relevant concentrations of biochemical factors and channel dimensions. In our model, the purple region representing the cytoplasmic periphery is treated as a compartmentalized volume containing both noninteracting Nup and transport receptor–interacting FG Nup agents. The central channel (blue) and nuclear basket (green) regions are analogously represented by compartmentalized volumes and functionalized with Nup and FG Nup agents. Gray regions of the NPC diagram represent the scaffold and nuclear envelope regions of the model that are impermeable to diffusing species.
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Figure 9: A cartoon representation of the NPC's environment (not to scale) projected onto a two-dimensional, on-lattice ABM with agents (spheres) representing protein factors. These agents move within the system and interact with other agents within their von Neumann neighborhood. One such neighborhood of cells is highlighted in gray for the smaller green agent that is pointed to by an arrow. The actual model consists of a 3D representation of the NPC structure and physiologically relevant concentrations of biochemical factors and channel dimensions. In our model, the purple region representing the cytoplasmic periphery is treated as a compartmentalized volume containing both noninteracting Nup and transport receptor–interacting FG Nup agents. The central channel (blue) and nuclear basket (green) regions are analogously represented by compartmentalized volumes and functionalized with Nup and FG Nup agents. Gray regions of the NPC diagram represent the scaffold and nuclear envelope regions of the model that are impermeable to diffusing species.

Mentions: In their simplest form, on-lattice ABMs consist of a mesh of “cells” that assemble the discretized space that agents occupy (Figure 9). The agents occupy these cells and are typically aware only of other agents within their “neighborhood” of cells, with the simplest neighborhood consisting of adjacent cells. Agents can be given the ability to move into adjacent cells and interact with other agents with some probability in conjunction with governing rules that define what movement and interactions are possible. On-lattice ABMs have been applied to biological systems involving diffusion, binding, and unbinding (Bonchev et al., 2010; Devillers et al., 2010; Dong et al., 2010).


An agent-based model for mRNA export through the nuclear pore complex.

Azimi M, Bulat E, Weis K, Mofrad MR - Mol. Biol. Cell (2014)

A cartoon representation of the NPC's environment (not to scale) projected onto a two-dimensional, on-lattice ABM with agents (spheres) representing protein factors. These agents move within the system and interact with other agents within their von Neumann neighborhood. One such neighborhood of cells is highlighted in gray for the smaller green agent that is pointed to by an arrow. The actual model consists of a 3D representation of the NPC structure and physiologically relevant concentrations of biochemical factors and channel dimensions. In our model, the purple region representing the cytoplasmic periphery is treated as a compartmentalized volume containing both noninteracting Nup and transport receptor–interacting FG Nup agents. The central channel (blue) and nuclear basket (green) regions are analogously represented by compartmentalized volumes and functionalized with Nup and FG Nup agents. Gray regions of the NPC diagram represent the scaffold and nuclear envelope regions of the model that are impermeable to diffusing species.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 9: A cartoon representation of the NPC's environment (not to scale) projected onto a two-dimensional, on-lattice ABM with agents (spheres) representing protein factors. These agents move within the system and interact with other agents within their von Neumann neighborhood. One such neighborhood of cells is highlighted in gray for the smaller green agent that is pointed to by an arrow. The actual model consists of a 3D representation of the NPC structure and physiologically relevant concentrations of biochemical factors and channel dimensions. In our model, the purple region representing the cytoplasmic periphery is treated as a compartmentalized volume containing both noninteracting Nup and transport receptor–interacting FG Nup agents. The central channel (blue) and nuclear basket (green) regions are analogously represented by compartmentalized volumes and functionalized with Nup and FG Nup agents. Gray regions of the NPC diagram represent the scaffold and nuclear envelope regions of the model that are impermeable to diffusing species.
Mentions: In their simplest form, on-lattice ABMs consist of a mesh of “cells” that assemble the discretized space that agents occupy (Figure 9). The agents occupy these cells and are typically aware only of other agents within their “neighborhood” of cells, with the simplest neighborhood consisting of adjacent cells. Agents can be given the ability to move into adjacent cells and interact with other agents with some probability in conjunction with governing rules that define what movement and interactions are possible. On-lattice ABMs have been applied to biological systems involving diffusion, binding, and unbinding (Bonchev et al., 2010; Devillers et al., 2010; Dong et al., 2010).

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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, Graduate Program in Chemical Biology, Berkeley, Berkeley, CA 94720.

Show MeSH
Related in: MedlinePlus