eRF1 mediates codon usage effects on mRNA translation efficiency through premature termination at rare codons

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Codon usage bias is a widespread phenomenon in genomes, crucial for regulating gene expression.
• The precise mechanisms by which codon usage impacts mRNA translation efficiency remain incompletely understood.

Purpose of the Study:

• To elucidate the role of codon usage in regulating mRNA translation efficiency and protein expression levels.
• To investigate the molecular mechanisms underlying codon usage-mediated translation regulation.

Main Methods:

• Analysis of ribosome profiling data in Neurospora and Drosophila cells.
• Investigation of ribosome stalling, translation elongation rates, and premature translation termination.
• Functional studies involving the translation termination factor eRF1.

Main Results:

• Rare codons significantly slow down translation elongation rates compared to common codons across all codon families.
• Ribosome stalling on rare codons can lead to premature translation termination, independent of protein sequence context.
• The translation termination factor eRF1 mediates rare codon-dependent premature termination by recognizing stalled ribosomes.
• Silencing eRF1 expression alters protein expression in a manner dependent on codon usage.

Conclusions:

• Codon usage directly regulates mRNA translation efficiency by modulating translation elongation rates and fidelity.
• A novel mechanism involving rare codon-induced ribosome stalling and eRF1-mediated premature termination is established.
• This codon usage regulatory mechanism is conserved between Neurospora and Drosophila, highlighting its biological significance.