Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes
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 r...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/125168 |
| _version_ | 1826200453181865984 |
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| author | Taggart, James C. Li, Gene-Wei |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Taggart, James C. Li, Gene-Wei |
| author_sort | Taggart, James C. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:36:42Z |
| format | Article |
| id | mit-1721.1/125168 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:36:42Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1251682022-10-01T04:46:53Z Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes Taggart, James C. Li, Gene-Wei Massachusetts Institute of Technology. Department of Biology 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. National Institutes of Health (U.S.) (Grant R35GM124732) National Institutes of Health (U.S.). Pre-Doctoral Training Grant (T32 GM007287) 2020-05-12T11:45:50Z 2020-05-12T11:45:50Z 2018-12 2020-01-23T17:42:29Z Article http://purl.org/eprint/type/JournalArticle 2405-4720 2405-4712 https://hdl.handle.net/1721.1/125168 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) en 10.1016/J.CELS.2018.11.003 Cell systems Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Taggart, James C. Li, Gene-Wei Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes |
| title | Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes |
| title_full | Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes |
| title_fullStr | Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes |
| title_full_unstemmed | Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes |
| title_short | Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes |
| title_sort | production of protein complex components is stoichiometric and lacks general feedback regulation in eukaryotes |
| url | https://hdl.handle.net/1721.1/125168 |
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