Systemic Reprogramming of Translation Efficiencies on Oxygen Stimulus

J J David Ho; Miling Wang; Timothy E Audas; Deukwoo Kwon; Steven K Carlsson; Sara Timpano; Sonia L Evagelou; Shaun Brothers; Mark L Gonzalgo; Jonathan R Krieger; Steven Chen; James Uniacke; Stephen Lee

doi:10.1016/j.celrep.2016.01.036

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Systemic Reprogramming of Translation Efficiencies on Oxygen Stimulus

Journal article

Open access

Peer reviewed

Systemic Reprogramming of Translation Efficiencies on Oxygen Stimulus

J J David Ho, Miling Wang, Timothy E Audas, Deukwoo Kwon, Steven K Carlsson, Sara Timpano, Sonia L Evagelou, Shaun Brothers, Mark L Gonzalgo, Jonathan R Krieger, …

Cell reports (Cambridge), Vol.14(6), pp.1293-1300

2016-02-16

DOI: https://doi.org/10.1016/j.celrep.2016.01.036

PMID: 26854219

Abstract

Oxygen - pharmacology

Epithelial Cells - metabolism

Epithelial Cells - drug effects

Humans

RNA, Messenger - genetics

Eukaryotic Initiation Factor-4F - genetics

RNA, Messenger - metabolism

Eukaryotic Initiation Factor-4F - metabolism

Neuroglia - drug effects

Cell Hypoxia

Neuroglia - cytology

Cell Line, Tumor

Neuroglia - metabolism

Protein Biosynthesis - drug effects

Epithelial Cells - cytology

Evolution, Molecular

Protein concentrations evolve under greater evolutionary constraint than mRNA levels. Translation efficiency of mRNA represents the chief determinant of basal protein concentrations. This raises a fundamental question of how mRNA and protein levels are coordinated in dynamic systems responding to physiological stimuli. This report examines the contributions of mRNA abundance and translation efficiency to protein output in cells responding to oxygen stimulus. We show that changes in translation efficiencies, and not mRNA levels, represent the major mechanism governing cellular responses to [O2] perturbations. Two distinct cap-dependent protein synthesis machineries select mRNAs for translation: the normoxic eIF4F and the hypoxic eIF4F(H). O2-dependent remodeling of translation efficiencies enables cells to produce adaptive translatomes from preexisting mRNA pools. Differences in mRNA expression observed under different [O2] are likely neutral, given that they occur during evolution. We propose that mRNAs contain translation efficiency determinants for their triage by the translation apparatus on [O2] stimulus.

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Title: Systemic Reprogramming of Translation Efficiencies on Oxygen Stimulus
Creators: J J David Ho - Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 31336, USA
Miling Wang - Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 31336, USA
Timothy E Audas - Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 31336, USA
Deukwoo Kwon - Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Biostatistics and Bioinformatics Core, Miller School of Medicine, University of Miami, Miami, FL 31336, USA
Steven K Carlsson - Center for Therapeutic Innovation, Miller School of Medicine, University of Miami, Miami, FL 31336, USA
Sara Timpano - Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON N1G 2W1, Canada
Sonia L Evagelou - Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON N1G 2W1, Canada
Shaun Brothers - Center for Therapeutic Innovation, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Department of Psychiatry, Miller School of Medicine, University of Miami, Miami, FL 31336, USA
Mark L Gonzalgo - Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 31336, USA
Jonathan R Krieger - SPARC BioCentre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
Steven Chen - Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Biostatistics and Bioinformatics Core, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 31336, USA
James Uniacke - Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON N1G 2W1, Canada
Stephen Lee - Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 31336, USA; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada. Electronic address: stephenlee@med.miami.edu
Publication Details: Cell reports (Cambridge), Vol.14(6), pp.1293-1300
Publisher: United States
Grant note: Canadian Institutes of Health Research 1R01CA200676 / NCI NIH HHS 1R01GM115342 / NIGMS NIH HHS R01 GM115342 / NIGMS NIH HHS R01 CA200676 / NCI NIH HHS
Academic Unit: UMMG Department of Urology; Miller School of Medicine; CoE - Electrical & Computer Engineering; UMMG Department of Public Health Sciences Research; College of Engineering; UMMG Dept of Psychiatry & Behavioral Sciences; Biochemistry & Molecular Biology Research
Language: English
Resource Type: Journal article
PMID: 26854219
Record Identifier: 991031559659202976