Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies
Heterogeneity of the main ribosomal composition represents an emerging, yet debatable, mechanism of gene expression regulation with a purported role in ribosomopathies, a group of disorders caused by mutations in ribosomal protein genes (RPs). Ribosomopathies, mysteriously relate with tissue-specifi...
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Frontiers Media S.A.
2022-02-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.805541/full |
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| author | Christos I. Papagiannopoulos Konstantinos A. Kyritsis Konstantina Psatha Konstantina Psatha Konstantina Psatha Konstantina Psatha Dimitra Mavridou Dimitra Mavridou Fani Chatzopoulou Fani Chatzopoulou Georgia Orfanoudaki Michalis Aivaliotis Michalis Aivaliotis Michalis Aivaliotis Michalis Aivaliotis Ioannis S. Vizirianakis Ioannis S. Vizirianakis Ioannis S. Vizirianakis |
| author_facet | Christos I. Papagiannopoulos Konstantinos A. Kyritsis Konstantina Psatha Konstantina Psatha Konstantina Psatha Konstantina Psatha Dimitra Mavridou Dimitra Mavridou Fani Chatzopoulou Fani Chatzopoulou Georgia Orfanoudaki Michalis Aivaliotis Michalis Aivaliotis Michalis Aivaliotis Michalis Aivaliotis Ioannis S. Vizirianakis Ioannis S. Vizirianakis Ioannis S. Vizirianakis |
| author_sort | Christos I. Papagiannopoulos |
| collection | DOAJ |
| description | Heterogeneity of the main ribosomal composition represents an emerging, yet debatable, mechanism of gene expression regulation with a purported role in ribosomopathies, a group of disorders caused by mutations in ribosomal protein genes (RPs). Ribosomopathies, mysteriously relate with tissue-specific symptoms (mainly anemia and cancer predisposition), despite the ubiquitous expression and necessity of the associated RPs. An outstanding question that may shed light into disease pathogenicity and provide potential pharmacological interventions, is whether and how the ribosomal composition is modified during, the highly affected by RP mutations, process of erythroid differentiation. To address this issue, we analyzed ribosome stoichiometry using an established model of erythroid differentiation, through sucrose gradient ultracentrifugation and quantitative proteomics. We found that differentiation associates with an extensive reprogramming of the overall ribosomal levels, characterized by an increase in monosomes and a decrease in polysomes. However, by calculating a stoichiometry score for each independent ribosomal protein, we found that the main ribosomal architecture remained invariable between immature and differentiated cells. In total, none of the 78 Ribosomal Proteins (RPs- 74 core RPs, Rack1, Fau and 2 paralogs) detected was statistically different between the samples. This data was further verified through antibody-mediated quantification of 6 representative RPs. Moreover, bioinformatic analysis of whole cell proteomic data derived out of 4 additional models of erythropoiesis revealed that RPs were co-regulated across these cell types, too. In conclusion, ribosomes maintain an invariant protein stoichiometry during differentiation, thus excluding ribosome heterogeneity from a potential mechanism of toxicity in ribosomopathies and other erythroid disorders. |
| first_indexed | 2024-04-11T19:35:13Z |
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| last_indexed | 2024-04-11T19:35:13Z |
| publishDate | 2022-02-01 |
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| spelling | doaj.art-7dbd8079f61d48b3bf1a917842d2d83e2022-12-22T04:06:52ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-02-01910.3389/fmolb.2022.805541805541Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding RibosomopathiesChristos I. Papagiannopoulos0Konstantinos A. Kyritsis1Konstantina Psatha2Konstantina Psatha3Konstantina Psatha4Konstantina Psatha5Dimitra Mavridou6Dimitra Mavridou7Fani Chatzopoulou8Fani Chatzopoulou9Georgia Orfanoudaki10Michalis Aivaliotis11Michalis Aivaliotis12Michalis Aivaliotis13Michalis Aivaliotis14Ioannis S. Vizirianakis15Ioannis S. Vizirianakis16Ioannis S. Vizirianakis17Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, GreeceLaboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, GreeceFunctional Proteomics and Systems Biology (FunPATh)—Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Thessaloniki, GreeceLaboratory of Biochemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, GreeceBasic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, GreeceInstitute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion, GreeceFunctional Proteomics and Systems Biology (FunPATh)—Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Thessaloniki, GreeceLaboratory of Biochemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, GreeceLaboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, GreeceLaboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, GreeceInstitute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion, GreeceFunctional Proteomics and Systems Biology (FunPATh)—Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Thessaloniki, GreeceLaboratory of Biochemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, GreeceBasic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, GreeceInstitute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion, GreeceLaboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, GreeceFunctional Proteomics and Systems Biology (FunPATh)—Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Thessaloniki, GreeceDepartment of Life and Health Sciences, University of Nicosia, Nicosia, CyprusHeterogeneity of the main ribosomal composition represents an emerging, yet debatable, mechanism of gene expression regulation with a purported role in ribosomopathies, a group of disorders caused by mutations in ribosomal protein genes (RPs). Ribosomopathies, mysteriously relate with tissue-specific symptoms (mainly anemia and cancer predisposition), despite the ubiquitous expression and necessity of the associated RPs. An outstanding question that may shed light into disease pathogenicity and provide potential pharmacological interventions, is whether and how the ribosomal composition is modified during, the highly affected by RP mutations, process of erythroid differentiation. To address this issue, we analyzed ribosome stoichiometry using an established model of erythroid differentiation, through sucrose gradient ultracentrifugation and quantitative proteomics. We found that differentiation associates with an extensive reprogramming of the overall ribosomal levels, characterized by an increase in monosomes and a decrease in polysomes. However, by calculating a stoichiometry score for each independent ribosomal protein, we found that the main ribosomal architecture remained invariable between immature and differentiated cells. In total, none of the 78 Ribosomal Proteins (RPs- 74 core RPs, Rack1, Fau and 2 paralogs) detected was statistically different between the samples. This data was further verified through antibody-mediated quantification of 6 representative RPs. Moreover, bioinformatic analysis of whole cell proteomic data derived out of 4 additional models of erythropoiesis revealed that RPs were co-regulated across these cell types, too. In conclusion, ribosomes maintain an invariant protein stoichiometry during differentiation, thus excluding ribosome heterogeneity from a potential mechanism of toxicity in ribosomopathies and other erythroid disorders.https://www.frontiersin.org/articles/10.3389/fmolb.2022.805541/fullribosomopathiesribosomal proteinserythropoiesisproteomicsmass spectrometry |
| spellingShingle | Christos I. Papagiannopoulos Konstantinos A. Kyritsis Konstantina Psatha Konstantina Psatha Konstantina Psatha Konstantina Psatha Dimitra Mavridou Dimitra Mavridou Fani Chatzopoulou Fani Chatzopoulou Georgia Orfanoudaki Michalis Aivaliotis Michalis Aivaliotis Michalis Aivaliotis Michalis Aivaliotis Ioannis S. Vizirianakis Ioannis S. Vizirianakis Ioannis S. Vizirianakis Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies Frontiers in Molecular Biosciences ribosomopathies ribosomal proteins erythropoiesis proteomics mass spectrometry |
| title | Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies |
| title_full | Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies |
| title_fullStr | Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies |
| title_full_unstemmed | Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies |
| title_short | Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies |
| title_sort | invariable ribosome stoichiometry during murine erythroid differentiation implications for understanding ribosomopathies |
| topic | ribosomopathies ribosomal proteins erythropoiesis proteomics mass spectrometry |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.805541/full |
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