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Ribosomopathies: how a common root can cause a tree of pathologies

Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple other factors are necessary for the processing...

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Autores principales: Danilova, Nadia, Gazda, Hanna T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582105/
https://www.ncbi.nlm.nih.gov/pubmed/26398160
http://dx.doi.org/10.1242/dmm.020529
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author Danilova, Nadia
Gazda, Hanna T.
author_facet Danilova, Nadia
Gazda, Hanna T.
author_sort Danilova, Nadia
collection PubMed
description Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple other factors are necessary for the processing of pre-rRNA, the assembly of ribosomal subunits, their export to the cytoplasm and for the final assembly of subunits into a ribosome. Haploinsufficiency of certain RPs causes DBA, whereas mutations in other factors cause various other ribosomopathies. Despite the general nature of their underlying defects, the clinical manifestations of ribosomopathies differ. In DBA, for example, red blood cell pathology is especially evident. In addition, individuals with DBA often have malformations of limbs, the face and various organs, and also have an increased risk of cancer. Common features shared among human DBA and animal models have emerged, such as small body size, eye defects, duplication or overgrowth of ectoderm-derived structures, and hematopoietic defects. Phenotypes of ribosomopathies are mediated both by p53-dependent and -independent pathways. The current challenge is to identify differences in response to ribosomal stress that lead to specific tissue defects in various ribosomopathies. Here, we review recent findings in this field, with a particular focus on animal models, and discuss how, in some cases, the different phenotypes of ribosomopathies might arise from differences in the spatiotemporal expression of the affected genes.
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spelling pubmed-45821052015-09-30 Ribosomopathies: how a common root can cause a tree of pathologies Danilova, Nadia Gazda, Hanna T. Dis Model Mech Review Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple other factors are necessary for the processing of pre-rRNA, the assembly of ribosomal subunits, their export to the cytoplasm and for the final assembly of subunits into a ribosome. Haploinsufficiency of certain RPs causes DBA, whereas mutations in other factors cause various other ribosomopathies. Despite the general nature of their underlying defects, the clinical manifestations of ribosomopathies differ. In DBA, for example, red blood cell pathology is especially evident. In addition, individuals with DBA often have malformations of limbs, the face and various organs, and also have an increased risk of cancer. Common features shared among human DBA and animal models have emerged, such as small body size, eye defects, duplication or overgrowth of ectoderm-derived structures, and hematopoietic defects. Phenotypes of ribosomopathies are mediated both by p53-dependent and -independent pathways. The current challenge is to identify differences in response to ribosomal stress that lead to specific tissue defects in various ribosomopathies. Here, we review recent findings in this field, with a particular focus on animal models, and discuss how, in some cases, the different phenotypes of ribosomopathies might arise from differences in the spatiotemporal expression of the affected genes. The Company of Biologists 2015-09-01 /pmc/articles/PMC4582105/ /pubmed/26398160 http://dx.doi.org/10.1242/dmm.020529 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Review
Danilova, Nadia
Gazda, Hanna T.
Ribosomopathies: how a common root can cause a tree of pathologies
title Ribosomopathies: how a common root can cause a tree of pathologies
title_full Ribosomopathies: how a common root can cause a tree of pathologies
title_fullStr Ribosomopathies: how a common root can cause a tree of pathologies
title_full_unstemmed Ribosomopathies: how a common root can cause a tree of pathologies
title_short Ribosomopathies: how a common root can cause a tree of pathologies
title_sort ribosomopathies: how a common root can cause a tree of pathologies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582105/
https://www.ncbi.nlm.nih.gov/pubmed/26398160
http://dx.doi.org/10.1242/dmm.020529
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