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Systemic Reprogramming of Translation Efficiencies on Oxygen Stimulus
J J David Ho1, Miling Wang1, Timothy E Audas1
1Department 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.
Cell Reports
|February 9, 2016
Summary
Cellular responses to oxygen levels are primarily driven by changes in translation efficiency, not mRNA levels. This allows cells to adapt by modifying protein synthesis from existing mRNA pools.
Area of Science:
- Molecular Biology
- Cellular Biology
- Evolutionary Biology
Background:
- Protein concentrations are under stronger evolutionary constraint than mRNA levels.
- Translation efficiency is a key factor determining basal protein concentrations.
- Understanding mRNA and protein coordination in dynamic cellular responses is crucial.
Purpose of the Study:
- To investigate the roles of mRNA abundance and translation efficiency in cellular protein output during oxygen stimulus.
- To elucidate the mechanisms coordinating mRNA and protein levels in response to physiological stimuli.
Main Methods:
- Analysis of cellular responses to oxygen perturbations.
- Examination of mRNA abundance and translation efficiency contributions to protein output.
- Identification of distinct protein synthesis machineries involved in normoxic and hypoxic conditions.
Main Results:
- Changes in translation efficiencies, rather than mRNA levels, are the primary drivers of cellular responses to oxygen fluctuations.
- Two distinct cap-dependent protein synthesis machineries, normoxic eIF4F and hypoxic eIF4F(H), select mRNAs for translation.
- Oxygen-dependent remodeling of translation efficiencies allows cells to generate adaptive translatomes from existing mRNA pools.
Conclusions:
- Cellular adaptation to oxygen stimuli relies on the modulation of translation efficiency.
- mRNA sequences may contain determinants for selective translation under oxygen stress.
- Observed differences in mRNA expression during evolution under varying oxygen levels might be neutral.
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