Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• Oxygen regulation of gene expression is crucial for basic science and therapeutics.
• Posttranslational modifications of ribosomal proteins are key to gene expression control.

Purpose of the Study:

• To investigate the role of oxygen in gene expression regulation.
• To identify the molecular mechanisms linking oxygen sensing to translation.

Main Methods:

• Mass spectrometric analysis of Saccharomyces cerevisiae ribosomes.
• Identification and characterization of RPS23 hydroxylases.
• Analysis of TPA1 deletion effects on translation termination efficiency.

Main Results:

• Discovered posttranslational hydroxylation of Rps23p (40S ribosomal protein) near the decoding center.
• Identified RPS23 hydroxylases as conserved eukaryotic Fe(II) and 2-oxoglutarate dependent oxygenases.
• Demonstrated that Rps23p hydroxylation modulates translational accuracy in a stop codon-dependent manner, impacting viability.

Conclusions:

• Rps23p hydroxylation directly links oxygenase catalysis to gene expression regulation at the translational level.
• This modification can increase or decrease translational accuracy, with implications for nonsense codon suppression.
• Findings provide a basis for developing small molecules to treat genetic diseases caused by nonsense mutations.