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Updated: Jun 29, 2025
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Analysis of Translation Initiation During Stress Conditions by Polysome Profiling
Published on: May 19, 2014
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Mitochondrial Ribosomal Protein MRPS15 Is a Component of Cytosolic Ribosomes and Regulates Translation in Stressed
Florian David1, Emilie Roussel1, Carine Froment2,3
1Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Unité Mixte de Recherche (UMR) 1297, Institut National de la Santé et de la Recherche Médicale (Inserm), Université de Toulouse, 31432 Toulouse, France.
International Journal of Molecular Sciences
|March 28, 2024
Summary
Stress impacts gene expression in heart cells. This study reveals mitochondrial ribosomal protein S15 (MRPS15) activates internal ribosome entry site (IRES)-dependent translation of specific mRNAs during cellular stress.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Cardiomyocyte Biology
Background:
- mRNA translation regulation is vital for gene expression control in stressed cells, particularly in pathologies like heart ischemia.
- Ribosome heterogeneity is an emerging mechanism governing the translation of specific mRNA subsets.
Purpose of the Study:
- To investigate ribosome composition changes in human cardiomyocytes under endoplasmic reticulum stress.
- To identify the role of specific ribosomal components in stress-induced translation regulation.
Main Methods:
- Human cardiomyocytes were subjected to tunicamycin-induced endoplasmic reticulum stress.
- Mass spectrometry was used to analyze translating ribosome composition.
- Proximity ligation assay (PLA), immunoprecipitation, and polysome profiling were employed.
Main Results:
- Endoplasmic reticulum stress inhibited global translation but activated internal ribosome entry site (IRES)-dependent translation.
- Mitochondrial ribosomal proteins (MRPs), notably MRPS15, were found in cytosolic polysomes with increased abundance in stressed cells.
- MRPS15 was confirmed as a ribosomal component crucial for activating IRES-dependent translation and specialized in translating unfolded protein response mRNAs.
Conclusions:
- Ribosome composition is altered during cellular stress, with MRPS15 playing a key role.
- The MRPS15-containing ribosome is specifically involved in translating mRNAs related to the unfolded protein response.
- Findings highlight MRPS15 as a potential therapeutic target for stress-related cardiovascular diseases.
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