Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Papagiannopoulos, Christos I., Kyritsis, Konstantinos A., Psatha, Konstantina, Mavridou, Dimitra, Chatzopoulou, Fani, Orfanoudaki, Georgia, Aivaliotis, Michalis, Vizirianakis, Ioannis S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850788/
https://www.ncbi.nlm.nih.gov/pubmed/35187080
http://dx.doi.org/10.3389/fmolb.2022.805541
_version_ 1784652675629973504
author Papagiannopoulos, Christos I.
Kyritsis, Konstantinos A.
Psatha, Konstantina
Mavridou, Dimitra
Chatzopoulou, Fani
Orfanoudaki, Georgia
Aivaliotis, Michalis
Vizirianakis, Ioannis S.
author_facet Papagiannopoulos, Christos I.
Kyritsis, Konstantinos A.
Psatha, Konstantina
Mavridou, Dimitra
Chatzopoulou, Fani
Orfanoudaki, Georgia
Aivaliotis, Michalis
Vizirianakis, Ioannis S.
author_sort Papagiannopoulos, Christos I.
collection PubMed
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.
format Online
Article
Text
id pubmed-8850788
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-88507882022-02-18 Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies Papagiannopoulos, Christos I. Kyritsis, Konstantinos A. Psatha, Konstantina Mavridou, Dimitra Chatzopoulou, Fani Orfanoudaki, Georgia Aivaliotis, Michalis Vizirianakis, Ioannis S. Front Mol Biosci Molecular Biosciences 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. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8850788/ /pubmed/35187080 http://dx.doi.org/10.3389/fmolb.2022.805541 Text en Copyright © 2022 Papagiannopoulos, Kyritsis, Psatha, Mavridou, Chatzopoulou, Orfanoudaki, Aivaliotis and Vizirianakis. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Papagiannopoulos, Christos I.
Kyritsis, Konstantinos A.
Psatha, Konstantina
Mavridou, Dimitra
Chatzopoulou, Fani
Orfanoudaki, Georgia
Aivaliotis, Michalis
Vizirianakis, Ioannis S.
Invariable Ribosome Stoichiometry During Murine Erythroid Differentiation: Implications for Understanding Ribosomopathies
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 Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850788/
https://www.ncbi.nlm.nih.gov/pubmed/35187080
http://dx.doi.org/10.3389/fmolb.2022.805541
work_keys_str_mv AT papagiannopouloschristosi invariableribosomestoichiometryduringmurineerythroiddifferentiationimplicationsforunderstandingribosomopathies
AT kyritsiskonstantinosa invariableribosomestoichiometryduringmurineerythroiddifferentiationimplicationsforunderstandingribosomopathies
AT psathakonstantina invariableribosomestoichiometryduringmurineerythroiddifferentiationimplicationsforunderstandingribosomopathies
AT mavridoudimitra invariableribosomestoichiometryduringmurineerythroiddifferentiationimplicationsforunderstandingribosomopathies
AT chatzopouloufani invariableribosomestoichiometryduringmurineerythroiddifferentiationimplicationsforunderstandingribosomopathies
AT orfanoudakigeorgia invariableribosomestoichiometryduringmurineerythroiddifferentiationimplicationsforunderstandingribosomopathies
AT aivaliotismichalis invariableribosomestoichiometryduringmurineerythroiddifferentiationimplicationsforunderstandingribosomopathies
AT vizirianakisioanniss invariableribosomestoichiometryduringmurineerythroiddifferentiationimplicationsforunderstandingribosomopathies