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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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Kymographs of 20 replicate simulations of mRNA export using the default configuration of transport receptor/FG Nup affinity of 100 μM and nine transport receptors along the length of the mRNA. The blue lines represent the position of the 5′ end, and the red lines represent the position of the 3′ end. The NPC central channel is centered at z = 0 nm in each plot. Plots are distributed to show (A) 10 failed exports and (B) 10 successful exports.
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Figure 10: Kymographs of 20 replicate simulations of mRNA export using the default configuration of transport receptor/FG Nup affinity of 100 μM and nine transport receptors along the length of the mRNA. The blue lines represent the position of the 5′ end, and the red lines represent the position of the 3′ end. The NPC central channel is centered at z = 0 nm in each plot. Plots are distributed to show (A) 10 failed exports and (B) 10 successful exports.

Mentions: The locations of the 5′ and 3′ termini, along with the location of the randomly placed “hrp36 tag” agent, were tracked over the course of the simulation. Throughout the rest of the article, we referred to the data captured through these tracking methods as double- and single-tag data, respectively. To analyze these trajectories, kymographs were generated illustrating the location of the 5′ and 3′ termini of the mRNA over time (Figure 10). The trajectories were further analyzed to determine the fraction of partial and successful transports per configuration, along with mRNA residence times in the nuclear basket and central channel, for comparison with previous in vivo observations. In this context, partial transport was defined as the initiation of transport from either the 5′ or 3′ end of the mRNA but a failure in the export of the other end.


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

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

Kymographs of 20 replicate simulations of mRNA export using the default configuration of transport receptor/FG Nup affinity of 100 μM and nine transport receptors along the length of the mRNA. The blue lines represent the position of the 5′ end, and the red lines represent the position of the 3′ end. The NPC central channel is centered at z = 0 nm in each plot. Plots are distributed to show (A) 10 failed exports and (B) 10 successful exports.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230623&req=5

Figure 10: Kymographs of 20 replicate simulations of mRNA export using the default configuration of transport receptor/FG Nup affinity of 100 μM and nine transport receptors along the length of the mRNA. The blue lines represent the position of the 5′ end, and the red lines represent the position of the 3′ end. The NPC central channel is centered at z = 0 nm in each plot. Plots are distributed to show (A) 10 failed exports and (B) 10 successful exports.
Mentions: The locations of the 5′ and 3′ termini, along with the location of the randomly placed “hrp36 tag” agent, were tracked over the course of the simulation. Throughout the rest of the article, we referred to the data captured through these tracking methods as double- and single-tag data, respectively. To analyze these trajectories, kymographs were generated illustrating the location of the 5′ and 3′ termini of the mRNA over time (Figure 10). The trajectories were further analyzed to determine the fraction of partial and successful transports per configuration, along with mRNA residence times in the nuclear basket and central channel, for comparison with previous in vivo observations. In this context, partial transport was defined as the initiation of transport from either the 5′ or 3′ end of the mRNA but a failure in the export of the other end.

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