Dataset Information

Testing Models of mRNA Localization Reveals Robustness Regulated by Reducing Transport between Cells.

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-? 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.

SUBMITTER: Harrison JU

PROVIDER: S-EPMC6895595 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Testing Models of mRNA Localization Reveals Robustness Regulated by Reducing Transport between Cells.

Harrison Jonathan U JU Parton Richard M RM Davis Ilan I Baker Ruth E RE

Biophysical journal 20191024 11

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 signifi ...[more]

PMID: 31708163

Similar Datasets

Project description:In the case of a transport system obeying Michaelis-Menten kinetics, completely general relationships are shown to exist between the final ratio of internal and external substrate concentrations, alpha, and the V/Km ratios found in zero-trans-entry, zero-trans-exit and equilibrium-exchange experiments (where V is a maximum substrate flux and Km a substrate half-saturation constant). The proof depends on a new method of derivation proceeding from the form of the experimental data rather than, as has been the practice in kinetic analysis, from a hypothetical reaction scheme. These general relationships, which will be true of all mechanisms giving rise to a particular type of behaviour (here Michaelis-Menten kinetics), provide a test for internal consistency in a set of experimental data. Other relationships, which are specific, can be derived from individual reaction schemes, with the use of traditional procedures in kinetic analysis. The specific relationships include constants for infinite trans entry and exit in addition to constants involved in the general relationships. In conjunction, the general and specific relationships provide a stringent test of mechanism. A set of results that fails to satisfy the general relationships must be rejected; here systematic error or unexpected changes in the transport system in different experiments may have distorted the calculated constants, or the system may not actually obey Michaelis-Menten kinetics. Results in accord with the general relationships, on the other hand, can be applied in specific tests of mechanism. The usefulness of the theorem is illustrated in the cases of the glucose-transport and choline-transport systems of erythrocytes. Experimental results taken from several studies in the literature, which were in accord with hyperbolic substrate kinetics, had previously been shown to disagree with relationships derived for the carrier model, and the model was rejected. The new analysis shows that the data violated the general relationships and therefore cannot decide the issue. More recent results on the glucose-transport system satisfy the general relations and agree with the carrier model.

Dataset Information

Testing Models of mRNA Localization Reveals Robustness Regulated by Reducing Transport between Cells.

Publications

Testing Models of mRNA Localization Reveals Robustness Regulated by Reducing Transport between Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets