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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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Two graphs that capture the effect of NXF1/FG Nup affinity on the mRNA's nuclear basket and central channel residence times during successful export events. The graph on the left corresponds to what is observed through probes placed at 5′ and 3′ ends of the mRNA, and the graph on the right corresponds to what is observed through a single probe located randomly along the length of the mRNA. Error bars represent 1 SD.
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Figure 3: Two graphs that capture the effect of NXF1/FG Nup affinity on the mRNA's nuclear basket and central channel residence times during successful export events. The graph on the left corresponds to what is observed through probes placed at 5′ and 3′ ends of the mRNA, and the graph on the right corresponds to what is observed through a single probe located randomly along the length of the mRNA. Error bars represent 1 SD.

Mentions: Keeping the nine-NTR configuration constant, we then varied the affinity between NXF1 and FG Nups more meticulously (Figure 2), observing nonmonotonic behavior in the export efficiency. When mRNA-bound NXF1 had a dissociation constant of 200 μM, no transport was observed. Increasing the affinity incrementally toward 20 μM led to an increase in the percentage of simulations in which successful transport was observed. When affinity was increased further to 2 μM, however, this percentage plummeted (Figure 2, blue). For successful transport events, average residence times in the basket and central channel increased more or less monotonically with increasing affinities (Figure 3).


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

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

Two graphs that capture the effect of NXF1/FG Nup affinity on the mRNA's nuclear basket and central channel residence times during successful export events. The graph on the left corresponds to what is observed through probes placed at 5′ and 3′ ends of the mRNA, and the graph on the right corresponds to what is observed through a single probe located randomly along the length of the mRNA. Error bars represent 1 SD.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 3: Two graphs that capture the effect of NXF1/FG Nup affinity on the mRNA's nuclear basket and central channel residence times during successful export events. The graph on the left corresponds to what is observed through probes placed at 5′ and 3′ ends of the mRNA, and the graph on the right corresponds to what is observed through a single probe located randomly along the length of the mRNA. Error bars represent 1 SD.
Mentions: Keeping the nine-NTR configuration constant, we then varied the affinity between NXF1 and FG Nups more meticulously (Figure 2), observing nonmonotonic behavior in the export efficiency. When mRNA-bound NXF1 had a dissociation constant of 200 μM, no transport was observed. Increasing the affinity incrementally toward 20 μM led to an increase in the percentage of simulations in which successful transport was observed. When affinity was increased further to 2 μM, however, this percentage plummeted (Figure 2, blue). For successful transport events, average residence times in the basket and central channel increased more or less monotonically with increasing affinities (Figure 3).

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