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

mRNA export from the nucleus is an essential step in the expression of every protein- coding gene in eukaryotes, but many aspects of this process remain poorly understood. The density of export receptors that must bind an mRNA to ensure export, as well as how receptor distribution affects transport...

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Autores principales: Azimi, Mohammad, Bulat, Evgeny, Weis, Karsten, Mofrad, Mohammad R. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230623/
https://www.ncbi.nlm.nih.gov/pubmed/25253717
http://dx.doi.org/10.1091/mbc.E14-06-1065
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author Azimi, Mohammad
Bulat, Evgeny
Weis, Karsten
Mofrad, Mohammad R. K.
author_facet Azimi, Mohammad
Bulat, Evgeny
Weis, Karsten
Mofrad, Mohammad R. K.
author_sort Azimi, Mohammad
collection PubMed
description mRNA export from the nucleus is an essential step in the expression of every protein- coding gene in eukaryotes, but many aspects of this process remain poorly understood. The density of export receptors that must bind an mRNA to ensure export, as well as how receptor distribution affects transport dynamics, is not known. It is also unclear whether the rate-limiting step for transport occurs at the nuclear basket, in the central channel, or on the cytoplasmic face of the nuclear pore complex. Using previously published biophysical and biochemical parameters of mRNA export, we implemented a three-dimensional, coarse-grained, agent-based model of mRNA export in the nanosecond regime to gain insight into these issues. 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.
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spelling pubmed-42306232015-01-20 An agent-based model for mRNA export through the nuclear pore complex Azimi, Mohammad Bulat, Evgeny Weis, Karsten Mofrad, Mohammad R. K. Mol Biol Cell Articles mRNA export from the nucleus is an essential step in the expression of every protein- coding gene in eukaryotes, but many aspects of this process remain poorly understood. The density of export receptors that must bind an mRNA to ensure export, as well as how receptor distribution affects transport dynamics, is not known. It is also unclear whether the rate-limiting step for transport occurs at the nuclear basket, in the central channel, or on the cytoplasmic face of the nuclear pore complex. Using previously published biophysical and biochemical parameters of mRNA export, we implemented a three-dimensional, coarse-grained, agent-based model of mRNA export in the nanosecond regime to gain insight into these issues. 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. The American Society for Cell Biology 2014-11-05 /pmc/articles/PMC4230623/ /pubmed/25253717 http://dx.doi.org/10.1091/mbc.E14-06-1065 Text en © 2014 Azimi, Bulat, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Azimi, Mohammad
Bulat, Evgeny
Weis, Karsten
Mofrad, Mohammad R. K.
An agent-based model for mRNA export through the nuclear pore complex
title An agent-based model for mRNA export through the nuclear pore complex
title_full An agent-based model for mRNA export through the nuclear pore complex
title_fullStr An agent-based model for mRNA export through the nuclear pore complex
title_full_unstemmed An agent-based model for mRNA export through the nuclear pore complex
title_short An agent-based model for mRNA export through the nuclear pore complex
title_sort agent-based model for mrna export through the nuclear pore complex
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230623/
https://www.ncbi.nlm.nih.gov/pubmed/25253717
http://dx.doi.org/10.1091/mbc.E14-06-1065
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