核糖体病变 (Ribosomopathy)是核糖体 异常所致的遗传疾病 ,为核糖体蛋白质 或其他参与核糖体组装 的蛋白发生基因突变 而使其无法正常组装所致[ 1] [ 2] [ 3] 。已知核糖体病变导致的疾病包括多数的先天性纯红细胞再生障碍性贫血 (DBA)[ 2] 、某些肌肉萎缩症 [ 4] 、X染色体偶连 的先天性角化不良症 亚型[ 5] [ 6] 、特雷彻·柯林斯综合征 (TCS)[ 2] [ 7] 、舒-戴二氏综合征 (SDS)[ 8] 、某些骨髓增生异常综合征 、北美印第安儿童肝硬化 (NAIC)[ 9] 、孤立性先天无脾症 (ACAS)[ 9] [ 10] [ 11] [ 12] 、Bowen-Conradi综合征 (BWCNS)[ 13] [ 14] [ 15] [ 16] 、CHARGE联合畸形 与ANE综合征 等[ 17] ,另外还有数种癌症 可能为核糖体异常所致[ 18] 。许多疾病的致病机理与核糖体异常激活p53 途径有关[ 19] [ 20] 。
核糖体组装的过程,每一步骤的异常都可能导致核糖体病变而致病
真核生物 组装核糖体的过程首先为在核仁 中由RNA聚合酶I 转录 产生45S 的前核糖体RNA (pre-rRNA),此RNA经剪切后可产生32S rRNA与30S rRNA,前者可再被剪切成28S rRNA 及5.8S rRNA [ 21] [ 22] ,后者则可被剪切成18S rRNA [ 23] ,28S、5.8S与独立由RNA聚合酶III 转录产生的5S rRNA 可与核糖体蛋白组合成60S核糖体亚基 [ 24] ,18S rRNA则与核糖体蛋白组合成40S核糖体亚基 ,翻译进行时两者再进一步结合产生80S核糖体 。此过程中各步骤的异常都可能影响核糖体组装而导致核糖体病变。
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^ OMIM 300126
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