Post-Translational Dosage Compensation Buffers Genetic Perturbations to Stoichiometry of Protein Complexes.

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.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Ishikawa K,Makanae K,Iwasaki S,Ingolia NT,Moriya H

doi

10.1371/journal.pgen.1006554

subject

Has Abstract

pub_date

2017-01-25 00:00:00

pages

e1006554

issue

1

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-16-02033

journal_volume

13

pub_type

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