Aguissa-Touré Almass-Houd, Da Costa Lydie, Leblanc Thierry, Tchernia Gil, Fribourg Sébastien, Gleizes Pierre-Emmanuel
Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse et CNRS, 118, route de Narbonne, 31062 Toulouse, France.
Med Sci (Paris). 2009 Jan;25(1):69-76. doi: 10.1051/medsci/200925169.
Diamond-Blackfan anemia (DBA), a rare congenital erythroblastopenia, has recently become a paradigm for a growing set of genetic diseases linked to mutations in genes encoding ribosomal proteins or factors involved in ribosome biogenesis. Recent studies of the structure and the function of ribosomal proteins affected in DBA indicate that their mutation in DBA primarily impacts ribosome biogenesis. Accordingly, cells from DBA patients display anomalies in the maturation of ribosomal RNAs. The explanation of this unexpected link between ribosome biogenesis, a ubiquitous process, and a disease mostly affecting erythroid differentiation may stem in part from the emerging concept of ribosomal stress response, a signaling pathway triggering cell cycle arrest in response to a defect in ribosome synthesis. Future studies of DBA and other diseases related to defects in ribosome biogenesis are likely to rapidly provide important insights into the regulatory mechanisms linking cell cycle progression to this major metabolic pathway.
钻石黑范贫血(DBA)是一种罕见的先天性成红细胞减少症,最近已成为越来越多与编码核糖体蛋白或参与核糖体生物合成的因子发生突变相关的遗传疾病的范例。最近对DBA中受影响的核糖体蛋白的结构和功能的研究表明,它们在DBA中的突变主要影响核糖体生物合成。因此,DBA患者的细胞在核糖体RNA成熟过程中表现出异常。核糖体生物合成是一个普遍存在的过程,而一种主要影响红细胞分化的疾病之间这种意外联系的解释可能部分源于核糖体应激反应这一新兴概念,核糖体应激反应是一种信号通路,可响应核糖体合成缺陷触发细胞周期停滞。未来对DBA和其他与核糖体生物合成缺陷相关疾病的研究可能会迅速为将细胞周期进程与这一主要代谢途径联系起来的调控机制提供重要见解。