Proteomics

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Mitochondrial ribosomal protein MRPS15 Is a component of cytosolic ribosomes and regulates translation in stressed cardiomyocytes


ABSTRACT: Regulation of mRNA translation is a crucial step in controlling gene expression in stressed cells, impacting many pathologies, including heart ischemia. In recent years, ribosome heterogeneity has emerged as a key control mechanism driving the translation of subsets of mRNAs. In this study, we investigated variations in ribosome composition in human cardiomyocytes subjected to endoplasmic reticulum stress induced by tunicamycin treatment. Our findings demonstrate that this stress inhibits global translation in cardiomyocytes while activating IRES-dependent translation. Analysis of translating ribosome composition in stressed and unstressed cardiomyocytes was conducted using mass spectrometry. We observed no significant changes in ribosomal protein composition, but several mitochondrial ribosomal proteins (MRPs) were identified in cytosolic polysomes, showing drastic variations between stressed and unstressed cells. The most notable increase in polysomes of stressed cells was observed in MRPS15. Its interaction with ribosomal proteins was confirmed by proximity ligation assay (PLA) and immunoprecipitation, suggesting its intrinsic role as a ribosomal component during stress. Knock-down or overexpression experiments of MRPS15 revealed its role as an activator of IRES-dependent translation. Furthermore, polysome profiling after immunoprecipitation with anti-MRPS15 antibody revealed that the “MRPS15 ribosome” is specialized in translating mRNAs involved in the unfolded protein response.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Carine Froment  

LAB HEAD: Anne-Catherine Prats

PROVIDER: PXD050321 | Pride | 2024-06-23

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
OFCCF200612_11.raw Raw
OFCCF200612_11_Polysome_unt_P1_Inj1.msf Msf
OFCCF200612_13.raw Raw
OFCCF200612_13_Polysome_unt_P3_Inj1.msf Msf
OFCCF200612_15.raw Raw
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Publications

Mitochondrial Ribosomal Protein MRPS15 Is a Component of Cytosolic Ribosomes and Regulates Translation in Stressed Cardiomyocytes.

David Florian F   Roussel Emilie E   Froment Carine C   Draia-Nicolau Tangra T   Pujol Françoise F   Burlet-Schiltz Odile O   Henras Anthony K AK   Lacazette Eric E   Morfoisse Florent F   Tatin Florence F   Diaz Jean-Jacques JJ   Catez Frédéric F   Garmy-Susini Barbara B   Prats Anne-Catherine AC  

International journal of molecular sciences 20240313 6


Regulation of mRNA translation is a crucial step in controlling gene expression in stressed cells, impacting many pathologies, including heart ischemia. In recent years, ribosome heterogeneity has emerged as a key control mechanism driving the translation of subsets of mRNAs. In this study, we investigated variations in ribosome composition in human cardiomyocytes subjected to endoplasmic reticulum stress induced by tunicamycin treatment. Our findings demonstrate that this stress inhibits global  ...[more]

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