Small and Large Ribosomal Subunit Deficiencies Lead to Distinct Gene Expression Signatures that Reflect Cellular Growth Rate.
Cell Proliferation
Gene Expression Regulation, Fungal
Mutation
Protein Processing, Post-Translational
RNA, Fungal
/ genetics
RNA, Messenger
/ genetics
Ribosomal Proteins
/ genetics
Ribosome Subunits, Large, Eukaryotic
/ genetics
Ribosome Subunits, Small, Eukaryotic
/ genetics
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Time Factors
Transcriptome
40S
60S
gene expression
ribosome
ribosome concentration
ribosomopathy
specialized ribosome
translation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
03 01 2019
03 01 2019
Historique:
received:
10
05
2018
revised:
04
09
2018
accepted:
18
10
2018
pubmed:
7
12
2018
medline:
4
6
2019
entrez:
4
12
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30503772
pii: S1097-2765(18)30892-X
doi: 10.1016/j.molcel.2018.10.032
pmc: PMC6382079
mid: NIHMS1515260
pii:
doi:
Substances chimiques
RNA, Fungal
0
RNA, Messenger
0
Ribosomal Proteins
0
Saccharomyces cerevisiae Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
36-47.e10Subventions
Organisme : NIGMS NIH HHS
ID : DP2 GM119138
Pays : United States
Organisme : NHGRI NIH HHS
ID : P50 HG006193
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM128802
Pays : United States
Organisme : NHGRI NIH HHS
ID : RM1 HG006193
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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