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Differential translational efficiency of ENaC subunits during lung development
Gail Otulakowski1, Bijan Rafii, Hugh O'Brodovich
1CIHR Group in Lung Development, Research Institute of the Hospital for Sick Children, Programme in Lung Biology Research, 555 University Avenue, Toronto, ON, M5G 1X8 Canada. gail.otulakowski@sickkids.ca
American Journal of Respiratory Cell and Molecular Biology
|December 16, 2003
Summary
Investigating the epithelial sodium channel (ENaC), this study reveals differential mRNA translation efficiencies for its alpha, beta, and gamma subunits in fetal rat lungs. Perinatal events globally impact lung mRNA translation.
Area of Science:
- Physiology
- Molecular Biology
- Developmental Biology
Background:
- The epithelial sodium channel (ENaC) is crucial for sodium transport in epithelia.
- ENaC comprises alpha, beta, and gamma subunits, with alpha-subunit mRNA being notably abundant.
- Discrepancies between alpha-ENaC mRNA levels and protein stoichiometry suggest post-transcriptional regulation.
Purpose of the Study:
- To investigate the translational efficiency of ENaC subunit mRNAs during fetal lung development.
- To explore the role of 5'-untranslated regions (5'UTRs) in regulating alpha-ENaC translation.
- To determine the impact of perinatal events on lung mRNA translation.
Main Methods:
- Sucrose density gradient centrifugation to analyze polysome association of ENaC subunit mRNAs.
- Northern blot analysis to assess mRNA distribution.
- Comparison of translation across different developmental stages (fetal vs. postnatal).
Main Results:
- All three ENaC subunits (alpha, beta, gamma) are actively translated, associated with polysomes.
- The alpha-subunit mRNA exhibits significantly lower translational efficiency compared to beta and gamma subunits.
- Alternative 5'UTRs are utilized for alpha-ENaC during fetal development.
- Birth induces a global decrease in lung mRNA translation, but ENaC subunit mRNA translation is relatively preserved.
- Cell-specific translational effects were observed for other mRNAs (cytokeratin 18, vimentin).
Conclusions:
- Significant differences exist in the translational efficiencies of ENaC subunit mRNAs.
- Perinatal processes exert a global influence on lung mRNA translation.
- Post-transcriptional regulation, including translational control, plays a key role in ENaC subunit abundance.