Yuping Chen

All Publications

• Viscosity-dependent control of protein synthesis and degradation. Nature communications Chen, Y., Huang, J. H., Phong, C., Ferrell, J. E. 2024; 15 (1): 2149

  Abstract

  It has been proposed that the concentration of proteins in the cytoplasm maximizes the speed of important biochemical reactions. Here we have used Xenopus egg extracts, which can be diluted or concentrated to yield a range of cytoplasmic protein concentrations, to test the effect of cytoplasmic concentration on mRNA translation and protein degradation. We find that protein synthesis rates are maximal in ~1x cytoplasm, whereas protein degradation continues to rise to a higher optimal concentration of ~1.8x. We show that this difference in optima can be attributed to a greater sensitivity of translation to cytoplasmic viscosity. The different concentration optima could produce a negative feedback homeostatic system, where increasing the cytoplasmic protein concentration above the 1x physiological level increases the viscosity of the cytoplasm, which selectively inhibits translation and drives the system back toward the 1x set point.

  View details for DOI 10.1038/s41467-024-46447-w

  View details for PubMedID 38459041

  View details for PubMedCentralID 9597509

• Robust trigger wave speed in Xenopus cytoplasmic extracts. bioRxiv : the preprint server for biology Huang, J. H., Chen, Y., Huang, W. Y., Tabatabaee, S., Ferrell, J. E. 2023

  Abstract

  Self-regenerating trigger waves can spread rapidly through the crowded cytoplasm without diminishing in amplitude or speed, providing consistent, reliable, long-range communication. The macromolecular concentration of the cytoplasm varies in response to physiological and environmental fluctuations, raising the question of how or if trigger waves can robustly operate in the face of such fluctuations. Using Xenopus extracts, we found that mitotic and apoptotic trigger wave speeds are remarkably invariant. We derived a model that accounts for this robustness and for the eventual slowing at extremely high and low cytoplasmic concentrations. The model implies that the positive and negative effects of cytoplasmic concentration (increased reactant concentration vs. increased viscosity) are nearly precisely balanced. Accordingly, artificially maintaining a constant cytoplasmic viscosity during dilution abrogates this robustness. The robustness in trigger wave speeds may contribute to the reliability of the extremely rapid embryonic cell cycle.

  View details for DOI 10.1101/2023.12.22.573127

  View details for PubMedID 38187567

  View details for PubMedCentralID PMC10769400

• Protein homeostasis from diffusion-dependent control of protein synthesis and degradation. bioRxiv : the preprint server for biology Chen, Y., Huang, J. H., Phong, C., Ferrell, J. E. 2023

  Abstract

  It has been proposed that the concentration of proteins in the cytoplasm maximizes the speed of important biochemical reactions. Here we have used the Xenopus extract system, which can be diluted or concentrated to yield a range of cytoplasmic protein concentrations, to test the effect of cytoplasmic concentration on mRNA translation and protein degradation. We found that protein synthesis rates are maximal in ~1x cytoplasm, whereas protein degradation continues to rise to an optimal concentration of ~1.8x. This can be attributed to the greater sensitivity of translation to cytoplasmic viscosity, perhaps because it involves unusually large macromolecular complexes like polyribosomes. The different concentration optima sets up a negative feedback homeostatic system, where increasing the cytoplasmic protein concentration above the 1x physiological level increases the viscosity of the cytoplasm, which selectively inhibits translation and drives the system back toward the 1x set point.

  View details for DOI 10.1101/2023.04.24.538146

  View details for PubMedID 37162886

  View details for PubMedCentralID PMC10168264

• C. elegans colony formation as a condensation phenomenon. Nature communications Chen, Y., Ferrell, J. E. 2021; 12 (1): 4947

  Abstract

  Phase separation at the molecular scale affects many biological processes. The theoretical requirements for phase separation are fairly minimal, and there is growing evidence that analogous phenomena occur at other scales in biology. Here we examine colony formation in the nematode C. elegans as a possible example of phase separation by a population of organisms. The population density of worms determines whether a colony will form in a thresholded fashion, and a simple two-compartment ordinary differential equation model correctly predicts the threshold. Furthermore, small, round colonies sometimes fuse to form larger, round colonies, and a phenomenon akin to Ostwald ripening - a coarsening process seen in many systems that undergo phase separation - also occurs. These findings support the emerging view that the principles of microscopic phase separation can also apply to collective behaviors of living organisms.

  View details for DOI 10.1038/s41467-021-25244-9

  View details for PubMedID 34400648

• Scaling gene expression for cell size control and senescence in Saccharomyces cerevisiae. Current genetics Chen, Y., Futcher, B. 2020

  Abstract

  Cells divide with appropriate frequency by coupling division to growth-that is, cells divide only when they have grown sufficiently large. This process is poorly understood, but has been studied using cell size mutants. In principle, mutations affecting cell size could affect the mean size ("set-point" mutants), or they could affect the variability of sizes ("homeostasis" mutants). In practice, almost all known size mutants affect set-point, with little effect on size homeostasis. One model for size-dependent division depends on a size-dependent gene expression program: Activators of cell division are over-expressed at larger and larger sizes, while inhibitors are under-expressed. At sufficiently large size, activators overcome inhibitors, and the cell divides. Amounts of activators and inhibitors determine the set-point, but the gene expression program (the rate at which expression changes with cell size) determines the breadth of the size distribution (homeostasis). In this model, set-point mutants identify cell cycle activators and inhibitors, while homeostasis mutants identify regulators that couple expression of activators and inhibitors to size. We consider recent results suggesting that increased cell size causes senescence, and suggest that at very large sizes, an excess of DNA binding proteins leads to size induced senescence.

  View details for DOI 10.1007/s00294-020-01098-4

  View details for PubMedID 33151380