Summary
Ribosomopathies are diseases caused by defects in ribosome biogenesis or function, manifesting with tissue-specific phenotypes including bone marrow failure and cancer predisposition.
Key Points
- 1Ribosomopathies arise from ribosomal protein or biogenesis factor mutations
- 2p53 activation via RPL5/RPL11-MDM2 axis is central
- 3Tissue specificity despite essential gene defects
- 4Cancer predisposition from chronic stress
Ribosomopathies represent a paradox: mutations in universally essential ribosomes cause tissue-specific pathologies. Diamond-Blackfan Anemia (DBA) is the prototype, caused by RP gene mutations (RPS19, RPL5, RPL11). Free ribosomal proteins bind MDM2, stabilizing p53 and causing cell cycle arrest. Erythroid progenitors are exquisitely sensitive. Other ribosomopathies include Shwachman-Diamond Syndrome (SBDS mutations), Treacher Collins Syndrome (TCOF1), and 5q- Syndrome (RPS14 haploinsufficiency). The tissue specificity paradox is explained by varying ribosome requirements, specialized ribosomes, and extra-ribosomal functions of RPs. Cancer predisposition results from chronic stress selecting for p53 mutations.