Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits
Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits
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DOI：
10.1182/blood-2006-07-038232
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发表时间：
2007-02-01
期刊：
影响因子：
20.3
通讯作者：
Ellis, Steven R.
中科院分区：
文献类型：
--
作者：
Flygare, Johan;Aspesi, Anna;Ellis, Steven R.
Diamond-Blackfan贫血（DBA）通常表现为红细胞发育不全，通常在生命的第一年出现。目前已知在DBA中突变的唯一基因编码核糖体蛋白S19（RPS 19）。先前的研究表明，酵母RPS 19蛋白是40 S核糖体亚基成熟的特定步骤所必需的。我们的目的是确定人类RPS 19蛋白是否在40 S亚基成熟的类似步骤中起作用。在造血细胞系TF-1中通过siRNA降低RPS 19表达的研究表明，人RPS 19也是40 S核糖体亚基成熟中的特定步骤所需的。这种成熟缺陷可以通过研究核糖体合成途径中沿着的rRNA加工中间体来监测。对携带RPS 19突变的DBA患者骨髓CD 34（-）细胞中这些中间体的分析显示，与在RPS 19表达减少的TF-1细胞中观察到的类似，存在前rRNA加工缺陷。这种缺陷在患有RPS 19突变的DBA患者的CD 34（+）细胞中观察到的程度较低。
Diamond-Blackfan anemia (DBA) typically presents with red blood cell aplasia that usually manifests in the first year of life. The only gene currently known to be mutated in DBA encodes ribosomal protein S19 (RPS19). Previous studies have shown that the yeast RPS19 protein is required for a specific step in the maturation of 40S ribosomal subunits. Our objective here was to determine whether the human RPS19 protein functions at a similar step in 40S subunit maturation. Studies where RPS19 expression is reduced by siRNA in the hematopoietic cell line, TF-1, show that human RPS19 is also required for a specific step in the maturation of 40S ribosomal subunits. This maturation defect can be monitored by studying rRNA-processing intermediates along the ribosome synthesis pathway. Analysis of these intermediates in CD34(-) cells from the bone marrow of patients with DBA harboring mutations in RPS19 revealed a pre-rRNA-processing defect similar to that observed in TF-1 cells where RPS19 expression was reduced. This defect was observed to a lesser extent in CD34(+) cells from patients with DBA who have mutations in RPS19.