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Small and large ribosomal subunit deficiencies lead to distinct gene expression signatures that reflect cellular growth rate

Item Type:Article
Title:Small and large ribosomal subunit deficiencies lead to distinct gene expression signatures that reflect cellular growth rate
Creators Name:Cheng, Z. and Mugler, C.F. and Keskin, A. and Hodapp, S. and Chan, L.Y.L. and Weis, K. and Mertins, P. and Regev, A. and Jovanovic, M. and Brar, G.A.
Abstract:Levels of the ribosome, the conserved molecular machine that mediates translation, are tightly linked to cellular growth rate. In humans, ribosomopathies are diseases associated with cell-type-specific pathologies and reduced ribosomal protein (RP) levels. Because gene expression defects resulting from ribosome deficiency have not yet been experimentally defined, we systematically probed mRNA, translation, and protein signatures that were either unlinked from or linked to cellular growth rate in RP-deficient yeast cells. Ribosome deficiency was associated with altered translation of gene subclasses, and profound general secondary effects of RP loss on the spectrum of cellular mRNAs were seen. Among these effects, growth-defective 60S mutants increased synthesis of proteins involved in proteasome-mediated degradation, whereas 40S mutants accumulated mature 60S subunits and increased translation of ribosome biogenesis genes. These distinct signatures of protein synthesis suggest intriguing and currently mysterious differences in the cellular consequences of deficiency for small and large ribosomal subunits.
Keywords:Ribosome, Translation, 40S, 60S, Gene Expression, Ribosomopathy, Specialized Ribosome, Ribosome Concentration
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press (U.S.A.)
Volume:73
Number:1
Page Range:36-47
Date:3 January 2019
Official Publication:https://doi.org/10.1016/j.molcel.2018.10.032
PubMed:View item in PubMed

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