摘要 : Purpose of review Congenital or acquired ribosomopathies related to mutations or deletions in ribosomal proteins gene or ribosome-associated proteins exhibit defective ribosome biogenesis that expose the cell to translation defect... 展开 Purpose of review Congenital or acquired ribosomopathies related to mutations or deletions in ribosomal proteins gene or ribosome-associated proteins exhibit defective ribosome biogenesis that expose the cell to translation defects. The mechanisms leading to low translation rate, loss-of-translation fidelity and translation selectivity are reviewed. Recent findings New quantitative techniques to measure ribosome component stoichiometry reveal that the pool of ribosomes could be heterogeneous and/or decreased with a limited number of translationally competent ribosomes. During development or cell differentiation, the absence of specific ribosome components or their replacement by paralogs generate heterogeneous ribosomes that are specialized in the translation of specific mRNAs. Decreased ribosome content by defective biosynthesis of a subunit results in translation selectivity at the expense of short structured transcripts with high codon adaptation index. Activation of p53, as a witness of nucleolar stress associated with the hematological phenotype of ribosomopathies participates in translational reprogramming of the cell by interfering with cap-dependent translation. Summary Translation selectivity is a common feature of ribosomopathies. p53 is more selectively activated in ribosomopathies with erythroid phenotype. The discovery of its dual role in regulating transcriptional and translational program supports new therapeutic perspectives. 收起