Ribosomopathies: how a common root can cause a tree of pathologies.
Ribosomopathies: how a common root can cause a tree of pathologies.
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DOI：
10.1242/dmm.020529
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发表时间：
2015-09
影响因子：
4.3
通讯作者：
Gazda HT
中科院分区：
文献类型：
--
作者：
Danilova N;Gazda HT
核糖体生物发生缺陷与一组称为核糖体病的疾病有关，其中Diamond-Blackfan贫血（DBA）研究最多。核糖体由核糖体蛋白（RPs）和核糖体RNA （rRNA）组成。RPs和其他多种因子对于pre-rRNA的加工、核糖体亚基的组装、它们输出到细胞质以及亚基最终组装成核糖体是必需的。某些RPs的单倍性不足导致DBA，而其他因素的突变导致各种其他核糖体病。尽管其潜在缺陷的一般性质，核糖体病的临床表现不同。例如，在DBA中，红细胞病理尤为明显。此外，患有DBA的人往往四肢、面部和各种器官都有畸形，患癌症的风险也会增加。人类DBA和动物模型的共同特征出现了，如体型小，眼睛缺陷，外胚层衍生结构的重复或过度生长，以及造血缺陷。核糖体病变的表型由p53依赖性和非依赖性途径介导。目前的挑战是确定不同的核糖体应激反应的差异，导致各种核糖体病的特定组织缺陷。在这里，我们回顾了这一领域的最新发现，特别关注动物模型，并讨论了在某些情况下，核糖体病的不同表型可能是如何由受影响基因的时空表达差异引起的。摘要：本文回顾了钻石黑帆贫血的最新资料，并讨论了它们与其他核糖体疾病的联系。
Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple other factors are necessary for the processing of pre-rRNA, the assembly of ribosomal subunits, their export to the cytoplasm and for the final assembly of subunits into a ribosome. Haploinsufficiency of certain RPs causes DBA, whereas mutations in other factors cause various other ribosomopathies. Despite the general nature of their underlying defects, the clinical manifestations of ribosomopathies differ. In DBA, for example, red blood cell pathology is especially evident. In addition, individuals with DBA often have malformations of limbs, the face and various organs, and also have an increased risk of cancer. Common features shared among human DBA and animal models have emerged, such as small body size, eye defects, duplication or overgrowth of ectoderm-derived structures, and hematopoietic defects. Phenotypes of ribosomopathies are mediated both by p53-dependent and -independent pathways. The current challenge is to identify differences in response to ribosomal stress that lead to specific tissue defects in various ribosomopathies. Here, we review recent findings in this field, with a particular focus on animal models, and discuss how, in some cases, the different phenotypes of ribosomopathies might arise from differences in the spatiotemporal expression of the affected genes. Summary: This paper reviews recent data on Diamond Blackfan anemia and discusses them in connection with other ribosomopathies.