論文 - 詳細
| RRC ID | 47501 |
|---|---|
| 著者 | Ishikawa K, Makanae K, Iwasaki S, Ingolia NT, Moriya H. |
| タイトル | Post-Translational Dosage Compensation Buffers Genetic Perturbations to Stoichiometry of Protein Complexes. |
| ジャーナル | PLoS Genet |
| Abstract |
Understanding buffering mechanisms for various perturbations is essential for understanding robustness in cellular systems. Protein-level dosage compensation, which arises when changes in gene copy number do not translate linearly into protein level, is one mechanism for buffering against genetic perturbations. Here, we present an approach to identify genes with dosage compensation by increasing the copy number of individual genes using the genetic tug-of-war technique. Our screen of chromosome I suggests that dosage-compensated genes constitute approximately 10% of the genome and consist predominantly of subunits of multi-protein complexes. Importantly, because subunit levels are regulated in a stoichiometry-dependent manner, dosage compensation plays a crucial role in maintaining subunit stoichiometries. Indeed, we observed changes in the levels of a complex when its subunit stoichiometries were perturbed. We further analyzed compensation mechanisms using a proteasome-defective mutant as well as ribosome profiling, which provided strong evidence for compensation by ubiquitin-dependent degradation but not reduced translational efficiency. Thus, our study provides a systematic understanding of dosage compensation and highlights that this post-translational regulation is a critical aspect of robustness in cellular systems. |
| 巻・号 | 13(1) |
| ページ | e1006554 |
| 公開日 | 2017-1-1 |
| DOI | 10.1371/journal.pgen.1006554 |
| PII | PGENETICS-D-16-02033 |
| PMID | 28121980 |
| PMC | PMC5266272 |
| MeSH | Chromosomes, Fungal / genetics Dosage Compensation, Genetic* Gene Dosage Gene Expression Regulation, Fungal* Proteasome Endopeptidase Complex / genetics Proteasome Endopeptidase Complex / metabolism Protein Subunits / genetics Protein Subunits / metabolism Proteolysis* Ribosomes / genetics Ribosomes / metabolism Saccharomyces cerevisiae / genetics* Saccharomyces cerevisiae / metabolism |
| IF | 5.175 |
| 引用数 | 25 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 30 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 酵母 | BY22813 |