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Translational errors as an early event in prion conversion
1Institut de Génétique et Microbiologie, UMR CNRS C8621, Université Paris-Sud, Orsay, France.
Cellular and Molecular Biology (Noisy-Le-Grand, France)
|April 9, 2002
Summary
Prion conversion in yeast may be triggered by errors during protein synthesis. Antibiotic G418 increased both translation errors and prion formation, suggesting aberrant proteins contribute to prion diseases.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Protein Misfolding Diseases
Background:
- Prions are infectious proteins causing neurodegenerative diseases.
- The molecular mechanisms initiating prion conversion remain largely unknown.
- Current models focus on post-translational protein modifications.
Purpose of the Study:
- To investigate the potential role of co-translational events in prion formation.
- To test if errors during protein synthesis influence prion conversion.
- To analyze the effect of translation-inhibiting antibiotics on prion formation in Saccharomyces cerevisiae.
Main Methods:
- Utilized Saccharomyces cerevisiae and its Ure2p protein, which can adopt a prion conformation ([URE3] phenotype).
- Administered antibiotics G418 and cycloheximide to yeast cells.
- Quantified [URE3] prion conversion frequency and monitored translational error rates.
Main Results:
- G418 treatment increased both the rate of translational errors and the frequency of [URE3] prion conversion.
- Cycloheximide, which did not affect translational fidelity, had no impact on [URE3] induction.
- A correlation was observed between increased translational errors and prion conversion frequency.
Conclusions:
- Co-translational events, specifically translational errors, may play a role in initiating prion formation.
- Aberrant proteins arising from translation errors could contribute to prion conversion.
- This challenges the exclusive focus on post-translational mechanisms in prionogenesis.