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核糖体病变

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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英语Diamond–Blackfan anemia(DBA)[2]、某些肌肉萎缩症英语Muscle atrophy[4]X染色体偶连先天性角化不良症英语dyskeratosis congenita亚型[5][6]特雷彻·柯林斯综合征英语Treacher Collins syndrome(TCS)[2][7]舒-戴二氏症候群英语Shwachman–Diamond syndrome(SDS)[8]、某些骨髓增生异常症候群北美印第安儿童肝硬化英语North American Indian childhood cirrhosis(NAIC)[9]孤立性先天无脾症英语isolated congenital asplenia(ACAS)[9][10][11][12]Bowen-Conradi症候群英语Bowen–Conradi syndrome(BWCNS)[13][14][15][16]CHARGE联合畸形ANE症候群[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

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英语RNA polymerase I转录产生45S前核糖体RNA英语Preribosomal 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 rRNA5.8S 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,转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。

列表

核糖体异常
名称 染色体 基因型[25] 表型 突变蛋白质 异常步骤
DBA1[25] 19q13.2 OMIM 603474 OMIM 105650 RPS19英语RPS19 30S至18S[26]:291
DBA2 8p23-p22 未知 OMIM 606129
DBA3 10q22-q23 OMIM 602412 OMIM 610629 RPS24英语RPS24[27] 30S至18S[26]:291
DBA4 15q OMIM 180472 OMIM 612527 RPS17英语RPS17[28] 30S至18S[26]:291
DBA5 3q29-qter OMIM 180468 OMIM 612528 RPL35A英语RPL35A[29] 32S至5.8S/28S[26]:291
DBA6 1p22.1 OMIM 603634 OMIM 612561 RPL5英语RPL5[30] 32S至5.8S/28S[26]:291
DBA7 1p36.1-p35 OMIM 604175 OMIM 612562 RPL11英语RPL11[30] 32S至5.8S/28S[26]:291
DBA8 2p25 OMIM 603658 OMIM 612563 RPS7英语RPS7[30] 30S至18S[26]:291
DBA9 6p OMIM 603632 OMIM 613308 RPS10英语RPS10[25] 30S至18S[31]
DBA10 12q OMIM 603701 OMIM 613309 RPS26英语RPS26 30S至18S[32]
DBA11 17p13 OMIM 603704 OMIM 614900 RPS26英语RPS26 30S至18S[32]
DBA12 3p24 OMIM 604174 OMIM 615550 RPL15英语RPL15 45S至32S[33]
DBA13 14q OMIM 603633 OMIM 615909 RPS29英语RPS29
DKCX Xq28 OMIM 300126 OMIM 305000 dyskerin英语dyskerin 与H/ACA snoRNA以及端粒酶RNA组分结合[34]
TCS
5q- 5q33.1 OMIM 130620 OMIM 153550 RPS14英语RPS14 30S至18S[26]:291
SDS 7q11.21 OMIM 607444 OMIM 260400 SBDS英语SBDS 60S至80S[26]:291
CHH 9p13.3 OMIM 157660 OMIM 250250 RMRP英语RMRP 粒线体RNA剪接
NAIC 16q22.1 OMIM 607456 OMIM 604901 CIRH1A英语CIRH1A NOL11的结合受影响[35]
ICAS 3p22.1 OMIM 150370 OMIM 271400 RPSA英语RPSA
BWCNS 12p13.31 OMIM 611531 OMIM 211180 EMG1英语EMG1 18S至40S
CHARGE 8q12.1-q12.2或7q21.11 OMIM 608892 OMIM 214800 CHD7英语CHD7Semaphorin英语Semaphorin
ACES OMIM xxx OMIM xxx RBM28英语RBM28

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