Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes
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nihms-1039967.pdf
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Accepted version
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2.07 MB
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Adobe PDF
Checksum (MD5)
d2675738f0170afc86b8bd901d98eb45
Author(s)
Taggart, James C.
Li, Gene-Wei
Date Issued
December 2018
Journal
Cell systems
Publisher
Elsevier BV
Citation
Taggart, James C. and Gene-Wei Li. “Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes.” Cell systems 7 (2018): 580-589.e4 © 2018 The Author(s)
Version
Author's final manuscript
Abstract
Constituents of multiprotein complexes are required at well-defined levels relative to each other. However, it remains unknown whether eukaryotic cells typically produce precise amounts of subunits, or instead rely on degradation to mitigate imprecise production. Here, we quantified the production rates of multiprotein complexes in unicellular and multicellular eukaryotes using ribosome profiling. By resolving read-mapping ambiguities, which occur for a large fraction of ribosome footprints and distort quantitation accuracy in eukaryotes, we found that obligate components of multiprotein complexes are produced in proportion to their stoichiometry, indicating that their abundances are already precisely tuned at the synthesis level. By systematically interrogating the impact of gene dosage variations in budding yeast, we found a general lack of negative feedback regulation protecting the normally precise rates of subunit synthesis. These results reveal a core principle of proteome homeostasis and highlight the evolution toward quantitative control at every step in the central dogma.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELS.2018.11.003
