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
リソース情報
酵母 BY22813