title: An agent-based model for mRNA export through the nuclear pore complex.
abstract: 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.
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, Graduate Program in Chemical Biology, Berkeley, Berkeley, CA 94720.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Azimi
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, Graduate Program in Chemical Biology, Berkeley, Berkeley, CA 94720 Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Bulat
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720 Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Karsten
authors.initials: K
authors.lastname: Weis
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, Graduate Program in Chemical Biology, Berkeley, Berkeley, CA 94720 mofrad@berkeley.edu.
authors.forename: Mohammad R K
authors.initials: MR
authors.lastname: Mofrad
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D022022:Nuclear Pore / Q000737:chemistry* / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D034443:RNA Transport; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors
chemical_list: D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger