Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes

Autoři: Koji Ishikawa aff001;  Akari Ishihara aff002;  Hisao Moriya aff001
Působiště autorů: Research Core for Interdisciplinary Sciences, Okayama University, Okayama, Japan aff001;  Course of Agrochemical Bioscience, Faculty of Agriculture, Okayama University, Okayama, Japan aff002
Vyšlo v časopise: Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009091
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009091


Proper control of gene expression levels upon various perturbations is a fundamental aspect of cellular robustness. Protein-level dosage compensation is one mechanism buffering perturbations to stoichiometry of multiprotein complexes through accelerated proteolysis of unassembled subunits. Although N-terminal acetylation- and ubiquitin-mediated proteasomal degradation by the Ac/N-end rule pathway enables selective compensation of excess subunits, it is unclear how widespread this pathway contributes to stoichiometry control. Here we report that dosage compensation depends only partially on the Ac/N-end rule pathway. Our analysis of genetic interactions between 18 subunits and 12 quality control factors in budding yeast demonstrated that multiple E3 ubiquitin ligases and N-acetyltransferases are involved in dosage compensation. We find that N-acetyltransferases-mediated compensation is not simply predictable from N-terminal sequence despite their sequence specificity for N-acetylation. We also find that the compensation of Pop3 and Bet4 is due in large part to a minor N-acetyltransferase NatD. Furthermore, canonical NatD substrates histone H2A/H4 were compensated even in its absence, suggesting N-acetylation-independent stoichiometry control. Our study reveals the complexity and robustness of the stoichiometry control system.

Klíčová slova:

Control systems – Dosage compensation – Histones – Quality control – Ribonucleases – Stoichiometry – Ubiquitin ligases – Yeast


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