. 2020 Sep; 9(9):2080.
doi: 10.3390/cells9092080.

Ribosomopathies: New Therapeutic Perspectives

Emilien Orgebin 1 François Lamoureux 1 Bertrand Isidor 2 Céline Charrier 1 Benjamin Ory 1 Frédéric Lézot 1 Marc Baud'huin 1 
  • PMID: 32932838
  •     143 References


Ribosomopathies are a group of rare diseases in which genetic mutations cause defects in either ribosome biogenesis or function, given specific phenotypes. Ribosomal proteins, and multiple other factors that are necessary for ribosome biogenesis (rRNA processing, assembly of subunits, export to cytoplasm), can be affected in ribosomopathies. Despite the need for ribosomes in all cell types, these diseases result mainly in tissue-specific impairments. Depending on the type of ribosomopathy and its pathogenicity, there are many potential therapeutic targets. The present manuscript will review our knowledge of ribosomopathies, discuss current treatments, and introduce the new therapeutic perspectives based on recent research. Diamond-Blackfan anemia, currently treated with blood transfusion prior to steroids, could be managed with a range of new compounds, acting mainly on anemia, such as L-leucine. Treacher Collins syndrome could be managed by various treatments, but it has recently been shown that proteasomal inhibition by MG132 or Bortezomib may improve cranial skeleton malformations. Developmental defects resulting from ribosomopathies could be also treated pharmacologically after birth. It might thus be possible to treat certain ribosomopathies without using multiple treatments such as surgery and transplants. Ribosomopathies remain an open field in the search for new therapeutic approaches based on our recent understanding of the role of ribosomes and progress in gene therapy for curing genetic disorders.

Keywords: riboprotein; ribosome; ribosomopathies; treatment.

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RAP-011 improves erythropoiesis in zebrafish model of Diamond-Blackfan anemia through antagonizing lefty1.
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Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia.
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TGFβ signaling underlies hematopoietic dysfunction and bone marrow failure in Shwachman-Diamond Syndrome.
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Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide.
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Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia.
Jorge Cortes, Hagop Kantarjian, +7 authors, Meir Wetzler.
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A Novel Mutation in RPL10 (Ribosomal Protein L10) Causes X-Linked Intellectual Disability, Cerebellar Hypoplasia, and Spondylo-Epiphyseal Dysplasia.
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RPL13 Variants Cause Spondyloepimetaphyseal Dysplasia with Severe Short Stature.
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Identification of RPS14 as a 5q- syndrome gene by RNA interference screen.
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Impaired ribosome biogenesis in Diamond-Blackfan anemia.
Valérie Choesmel, Daniel Bacqueville, +7 authors, Pierre-Emmanuel Gleizes.
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TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients.
Gisela Caceres, Kathy McGraw, +18 authors, Alan F List.
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Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis.
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Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anemia patients. DBA group of Société d'Hématologie et d'Immunologie Pédiatrique (SHIP), Gesellshaft für Pädiatrische Onkologie und Hämatologie (GPOH), and the European Society for Pediatric Hematology and Immunology (ESPHI).
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The Genetic Landscape of Diamond-Blackfan Anemia.
Jacob C Ulirsch, Jeffrey M Verboon, +39 authors, Hanna T Gazda.
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Novel and known ribosomal causes of Diamond-Blackfan anaemia identified through comprehensive genomic characterisation.
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J Med Genet, 2017 Mar 11; 54(6). PMID: 28280134
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Granulocyte colony-stimulating factor-responsive chronic neutropenia in cartilage-hair hypoplasia.
Roland A Ammann, Andrea Duppenthaler, Juergen Bux, Christoph Aebi.
J Pediatr Hematol Oncol, 2004 May 29; 26(6). PMID: 15167352
Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy.
Leonela Amoasii, John C W Hildyard, +10 authors, Eric N Olson.
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Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood.
Simon Edvardson, Claudia M Nicolae, +14 authors, Orly Elpeleg.
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Danazol Treatment for Telomere Diseases.
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Small and Large Ribosomal Subunit Deficiencies Lead to Distinct Gene Expression Signatures that Reflect Cellular Growth Rate.
Ze Cheng, Christopher Frederick Mugler, +7 authors, Gloria Ann Brar.
Mol Cell, 2018 Dec 07; 73(1). PMID: 30503772    Free PMC article.
A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis.
Pierre Chagnon, Jacques Michaud, +6 authors, Andrea Richter.
Am J Hum Genet, 2002 Nov 06; 71(6). PMID: 12417987    Free PMC article.
Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita.
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