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Diamond Blackfan anemia: ribosomal proteins going rogue
- Source :
- Seminars in Hematology, Seminars in Hematology, WB Saunders, 2011, 48 (2), pp.89-96. ⟨10.1053/j.seminhematol.2011.02.005⟩
- Publication Year :
- 2011
-
Abstract
- International audience; Within the decade following the demonstration that mutations in the RPS19 gene can lead to Diamond-Blackfan anemia (DBA), this disease has become a paradigm for an emerging group of pathologies linked to defects in ribosome biogenesis. DBA patients exhibit abnormal pre-rRNA maturation patterns and the majority bear mutations in one of several ribosomal protein genes that encode structural components of the ribosome essential for the correct assembly of the ribosomal subunits. Extensive study of the most frequently mutated gene, RPS19, has shown that mutations prevent the assembly of the ribosomal protein into forming pre-ribosomal particles. This defect in ribosome production triggers nucleolar stress pathways, the activation of which appears to be central to pathophysiological mechanisms. Why mutations in ribosomal protein genes so strongly and specifically affect erythropoiesis in DBA remains a challenging question, especially given the fact that defects in genes encoding nonstructural ribosome biogenesis factors have been shown to cause diseases other than DBA. A major problem in understanding the pathophysiological mechanisms in DBA remains the lack of a suitable animal model. Despite this, considerable strides have been made over that past few years demonstrating that several factors involved in the synthesis of ribosomes are targets of disease-causing mutations.
- Subjects :
- Ribosomal Proteins
Ribosome biogenesis
Biology
medicine.disease_cause
Ribosome
03 medical and health sciences
0302 clinical medicine
Ribosomal protein
medicine
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Diamond–Blackfan anemia
Gene
030304 developmental biology
Anemia, Diamond-Blackfan
Genetics
0303 health sciences
Mutation
Hematology
Ribosomal RNA
medicine.disease
3. Good health
030220 oncology & carcinogenesis
Erythropoiesis
Subjects
Details
- ISSN :
- 15328686 and 00371963
- Volume :
- 48
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Seminars in hematology
- Accession number :
- edsair.doi.dedup.....a434b21cd10c300680cad9060fa312d9