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Updated: Aug 12, 2026
09:16
Eukaryotic Polyribosome Profile Analysis
Published on: June 15, 2010
Selenocysteine codons decrease polysome association on endogenous selenoprotein mRNAs
1Thyroid Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|March 22, 2001
Summary
Selenocysteine incorporation is inefficient due to a translational penalty from UGA codons in selenoprotein mRNAs. Increased release factors may improve this process for selenoprotein synthesis.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- Selenocysteine incorporation into proteins is generally inefficient across various biological systems.
- Despite observed inefficiencies, animals produce full-length selenoproteins, suggesting natural processes differ from experimental findings.
Purpose of the Study:
- Investigate the discrepancy between observed and natural selenocysteine incorporation efficiency.
- Analyze ribosomal loading on selenoprotein mRNAs in mammalian cells.
Main Methods:
- Examined polysome profiles of endogenous selenoprotein mRNAs (type 1 deiodinase, glutathione peroxidase, selenoprotein P) in a mammalian cell line.
- Compared ribosomal loading with nonselenoprotein mRNAs.
- Substituted cysteine for selenocysteine codon in type 1 deiodinase mRNA.
- Assessed the impact of eukaryotic release factors eRF1 and eRF3 expression.
Main Results:
- Selenoprotein mRNAs (type 1 deiodinase, glutathione peroxidase, selenoprotein P) showed reduced ribosome loading compared to their predicted sizes.
- Ribosome numbers correlated with UGA selenocysteine codon termination.
- Replacing the selenocysteine codon with a cysteine codon normalized ribosomal loading.
- Increased expression of eukaryotic release factors eRF1 and eRF3 enhanced ribosomal loading.
Conclusions:
- The UGA selenocysteine codon imposes a translational penalty on selenoprotein mRNAs.
- Elevated levels of eukaryotic release factors may influence termination kinetics during selenoprotein synthesis.
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