Ribosomopathies: human disorders of ribosome dysfunction
Top Cited Papers
Open Access
- 22 April 2010
- journal article
- review article
- Published by American Society of Hematology in Blood
- Vol. 115 (16), 3196-3205
- https://doi.org/10.1182/blood-2009-10-178129
Abstract
Ribosomopathies compose a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical phenotypes. Congenital mutations in RPS19 and other genes encoding ribosomal proteins cause Diamond-Blackfan anemia, a disorder characterized by hypoplastic, macrocytic anemia. Mutations in other genes required for normal ribosome biogenesis have been implicated in other rare congenital syndromes, Schwachman-Diamond syndrome, dyskeratosis congenita, cartilage hair hypoplasia, and Treacher Collins syndrome. In addition, the 5q− syndrome, a subtype of myelodysplastic syndrome, is caused by a somatically acquired deletion of chromosome 5q, which leads to haploinsufficiency of the ribosomal protein RPS14 and an erythroid phenotype highly similar to Diamond-Blackfan anemia. Acquired abnormalities in ribosome function have been implicated more broadly in human malignancies. The p53 pathway provides a surveillance mechanism for protein translation as well as genome integrity and is activated by defects in ribosome biogenesis; this pathway appears to be a critical mediator of many of the clinical features of ribosomopathies. Elucidation of the mechanisms whereby selective abnormalities in ribosome biogenesis cause specific clinical syndromes will hopefully lead to novel therapeutic strategies for these diseases.Keywords
This publication has 107 references indexed in Scilit:
- A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q– syndromeNature Medicine, 2009
- Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotypeNature Medicine, 2009
- Treacher Collins syndrome: Unmasking the role of Tcof1/treacleThe International Journal of Biochemistry & Cell Biology, 2009
- Shwachman-Diamond Syndrome: A Review of the Clinical Presentation, Molecular Pathogenesis, Diagnosis, and TreatmentHematology/Oncology Clinics of North America, 2009
- Diamond-Blackfan Anemia: Diagnosis, Treatment, and Molecular PathogenesisHematology/Oncology Clinics of North America, 2009
- Dyskeratosis CongenitaHematology/Oncology Clinics of North America, 2009
- How Common Are Extraribosomal Functions of Ribosomal Proteins?Molecular Cell, 2009
- Ribosomal Protein L5 and L11 Mutations Are Associated with Cleft Palate and Abnormal Thumbs in Diamond-Blackfan Anemia PatientsAmerican Journal of Human Genetics, 2008
- Mdm2 Regulates p53 mRNA Translation through Inhibitory Interactions with Ribosomal Protein L26Molecular Cell, 2008
- Identification of RPS14 as a 5q- syndrome gene by RNA interference screenNature, 2008