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Viscosity-dependent control of protein synthesis and degradation

Author

Listed:
  • Yuping Chen

    (Stanford University School of Medicine)

  • Jo-Hsi Huang

    (Stanford University School of Medicine)

  • Connie Phong

    (Stanford University School of Medicine)

  • James E. Ferrell

    (Stanford University School of Medicine
    Stanford University School of Medicine)

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.

Suggested Citation

  • Yuping Chen & Jo-Hsi Huang & Connie Phong & James E. Ferrell, 2024. "Viscosity-dependent control of protein synthesis and degradation," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46447-w
    DOI: 10.1038/s41467-024-46447-w
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    References listed on IDEAS

    as
    1. Xiao-Pan Hu & Hugo Dourado & Peter Schubert & Martin J. Lercher, 2020. "The protein translation machinery is expressed for maximal efficiency in Escherichia coli," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    2. Björn Schwanhäusser & Dorothea Busse & Na Li & Gunnar Dittmar & Johannes Schuchhardt & Jana Wolf & Wei Chen & Matthias Selbach, 2011. "Global quantification of mammalian gene expression control," Nature, Nature, vol. 473(7347), pages 337-342, May.
    3. William Y. C. Huang & Xianrui Cheng & James E. Ferrell, 2022. "Cytoplasmic organization promotes protein diffusion in Xenopus extracts," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
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