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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 combined plot of end-to-end length averaged over 100 simulations for multiple affinity and nuclear transport receptor configurations in the ABM. Note that, where unspecified, the number of transport receptors was set to the baseline value of nine, distributed uniformly along the length of the mRNA. The x-axis represents the position along the axis perpendicular to the nuclear envelope (z-distance), with x = 0 set at the center of the central channel of the NPC. Left to right, the dashed lines represent the distal edge of the nuclear basket, the nuclear edge of the central channel, the cytoplasmic edge of the central channel, and the distal edge of the cytoplasmic filaments, respectively. Note that low sampling of successful transport events accounts for the increased observed variability in average end-to-end lengths of low Nup-NXF1– affinity transports on the cytoplasmic side.
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Figure 8: A combined plot of end-to-end length averaged over 100 simulations for multiple affinity and nuclear transport receptor configurations in the ABM. Note that, where unspecified, the number of transport receptors was set to the baseline value of nine, distributed uniformly along the length of the mRNA. The x-axis represents the position along the axis perpendicular to the nuclear envelope (z-distance), with x = 0 set at the center of the central channel of the NPC. Left to right, the dashed lines represent the distal edge of the nuclear basket, the nuclear edge of the central channel, the cytoplasmic edge of the central channel, and the distal edge of the cytoplasmic filaments, respectively. Note that low sampling of successful transport events accounts for the increased observed variability in average end-to-end lengths of low Nup-NXF1– affinity transports on the cytoplasmic side.

Mentions: Previous studies reported lengthening of the mRNA as it approaches the central channel (Daneholt, 1997). This observation was for the Balbiani ring mRNA, which is much larger than the mRNA modeled in our simulations (∼37 vs. ∼2.2 kb). Nevertheless, we wanted to explore whether such lengthening would be observed in our simulations. As shown in Figure 8, the average end-to-end length of mRNA approaching the basket dropped initially from that of the globular conformation taken on when diffusing freely throughout the nucleoplasm. This reduced end-to-end length appears to be the result of the mRNA taking on a more compact conformation as NXF1 proteins bind multiple Nups in the basket. Average end-to-end length then increased as the polymer translocated through the central channel. This behavior is consistent with what has been observed in EM studies of mRNA export. Of note, increased affinity and number of transport receptors both resulted in increased compaction of the mRNA polymer in the basket (Figure 8).


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 combined plot of end-to-end length averaged over 100 simulations for multiple affinity and nuclear transport receptor configurations in the ABM. Note that, where unspecified, the number of transport receptors was set to the baseline value of nine, distributed uniformly along the length of the mRNA. The x-axis represents the position along the axis perpendicular to the nuclear envelope (z-distance), with x = 0 set at the center of the central channel of the NPC. Left to right, the dashed lines represent the distal edge of the nuclear basket, the nuclear edge of the central channel, the cytoplasmic edge of the central channel, and the distal edge of the cytoplasmic filaments, respectively. Note that low sampling of successful transport events accounts for the increased observed variability in average end-to-end lengths of low Nup-NXF1– affinity transports on the cytoplasmic side.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 8: A combined plot of end-to-end length averaged over 100 simulations for multiple affinity and nuclear transport receptor configurations in the ABM. Note that, where unspecified, the number of transport receptors was set to the baseline value of nine, distributed uniformly along the length of the mRNA. The x-axis represents the position along the axis perpendicular to the nuclear envelope (z-distance), with x = 0 set at the center of the central channel of the NPC. Left to right, the dashed lines represent the distal edge of the nuclear basket, the nuclear edge of the central channel, the cytoplasmic edge of the central channel, and the distal edge of the cytoplasmic filaments, respectively. Note that low sampling of successful transport events accounts for the increased observed variability in average end-to-end lengths of low Nup-NXF1– affinity transports on the cytoplasmic side.
Mentions: Previous studies reported lengthening of the mRNA as it approaches the central channel (Daneholt, 1997). This observation was for the Balbiani ring mRNA, which is much larger than the mRNA modeled in our simulations (∼37 vs. ∼2.2 kb). Nevertheless, we wanted to explore whether such lengthening would be observed in our simulations. As shown in Figure 8, the average end-to-end length of mRNA approaching the basket dropped initially from that of the globular conformation taken on when diffusing freely throughout the nucleoplasm. This reduced end-to-end length appears to be the result of the mRNA taking on a more compact conformation as NXF1 proteins bind multiple Nups in the basket. Average end-to-end length then increased as the polymer translocated through the central channel. This behavior is consistent with what has been observed in EM studies of mRNA export. Of note, increased affinity and number of transport receptors both resulted in increased compaction of the mRNA polymer in the basket (Figure 8).

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