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Testing models of mRNA localization reveals robustness regulated by reducing transport between cells
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Harrison, Jonathan, Parton, Richard M., Davis, Ilan and Baker, Ruth E. (2019) Testing models of mRNA localization reveals robustness regulated by reducing transport between cells. Biophysical Journal, 117 (11). pp. 2154-2165. doi:10.1016/j.bpj.2019.10.025
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WRAP-testing-models-localization-robustness-cells-Harrison-2019.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only until 24 October 2020. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (7Mb) |
Official URL: http://doi.org/10.1016/j.bpj.2019.10.025
Abstract
Robust control of gene expression in both space and time is of central importance in the regulation of cellular processes and for multicellular development. However, the mechanisms by which robustness is achieved are generally not identified or well understood. For example, messenger RNA (mRNA) localization by molecular motor-driven transport is crucial for cell polarization in numerous contexts, but the regulatory mechanisms that enable this process to take place in the face of noise or significant perturbations are not fully understood. Here, we use a combined experimental-theoretical approach to characterize the robustness of gurken/transforming growth factor-α mRNA localization in Drosophila egg chambers, where the oocyte and 15 surrounding nurse cells are connected in a stereotypic network via intracellular bridges known as ring canals. We construct a mathematical model that encodes simplified descriptions of the range of steps involved in mRNA localization, including production and transport between and within cells until the final destination in the oocyte. Using Bayesian inference, we calibrate this model using quantitative single molecule fluorescence in situ hybridization data. By analyzing both the steady state and dynamic behaviors of the model, we provide estimates for the rates of different steps of the localization process as well as the extent of directional bias in transport through the ring canals. The model predicts that mRNA synthesis and transport must be tightly balanced to maintain robustness, a prediction that we tested experimentally using an overexpression mutant. Surprisingly, the overexpression mutant fails to display the anticipated degree of overaccumulation of mRNA in the oocyte predicted by the model. Through careful model-based analysis of quantitative data from the overexpression mutant, we show evidence of saturation of the transport of mRNA through ring canals. We conclude that this saturation engenders robustness of the localization process in the face of significant variation in the levels of mRNA synthesis.
| Item Type: | Journal Article | ||||||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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| Divisions: | Faculty of Science > Mathematics | ||||||||||||||||||||||||
| SWORD Depositor: | Library Publications Router | ||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Messenger RNA -- Mathematical models, Genetic regulation, Biological transport -- Regulation | ||||||||||||||||||||||||
| Journal or Publication Title: | Biophysical Journal | ||||||||||||||||||||||||
| Publisher: | Elsevier | ||||||||||||||||||||||||
| ISSN: | 0006-3495 | ||||||||||||||||||||||||
| Official Date: | 3 December 2019 | ||||||||||||||||||||||||
| Dates: |
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| Date of first compliant deposit: | 10 December 2019 | ||||||||||||||||||||||||
| Volume: | 117 | ||||||||||||||||||||||||
| Number: | 11 | ||||||||||||||||||||||||
| Page Range: | pp. 2154-2165 | ||||||||||||||||||||||||
| DOI: | 10.1016/j.bpj.2019.10.025 | ||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||
| Publisher Statement: | ** Article version: AM ** Embargo end date: 03-12-2020 ** From Elsevier via Jisc Publications Router ** History: accepted 15-10-2019; epub 03-12-2019; issue date 03-12-2019. ** Licence for AM version of this article starting on 03-12-2020: http://creativecommons.org/licenses/by-nc-nd/4.0/ | ||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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