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The activator/repressor Hap1 binds to the yeast eIF5A-encoding gene TIF51A to adapt its expression to the
Marina Barba-Aliaga1,2, Paula Alepuz1,2
1Instituto de Biotecnología y Biomedicina (Biotecmed), Universitat de València, Spain.
FEBS Letters
|May 1, 2022
Summary
Mitochondrial function relies on translation elongation factor eIF5A. This study reveals how transcription factor Hap1 regulates yeast eIF5A (eukaryotic initiation factor 5A) gene expression to match cellular energy needs.
Area of Science:
- Cellular Biology
- Molecular Biology
- Genetics
Background:
- Mitochondrial dysfunction is linked to aging and diseases.
- The translation elongation factor eIF5A is crucial for mitochondrial health.
- Yeast has two homologous genes for eIF5A: TIF51A and TIF51B.
Purpose of the Study:
- To investigate the regulation of eIF5A gene expression in yeast.
- To understand how eIF5A levels adapt to cellular metabolic states.
- To elucidate the role of transcription factor Hap1 in this process.
Main Methods:
- Analysis of transcription factor binding to gene promoters.
- Investigating gene expression under different metabolic conditions (respiration vs. nonrespiration).
- Identifying corepressor recruitment in gene regulation.
Main Results:
- Hap1 directly activates TIF51A expression during respiration and represses it during nonrespiration by recruiting Tup1.
- Hap1 indirectly regulates TIF51B by controlling repressor genes (ROX1, MOT3) under varying metabolic conditions.
- Yeast eIF5A isoform levels are dynamically adjusted based on mitochondrial activity.
Conclusions:
- Hap1 acts as a key regulator of eIF5A expression in yeast.
- This regulation ensures eIF5A levels are optimized for cellular energetic demands.
- The findings provide insights into maintaining mitochondrial function and its link to disease.
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