核糖體病變

核糖體病變(Ribosomopathy)是核糖體異常所致的遺傳疾病,為核糖體蛋白質或其他參與核糖體組裝的蛋白發生基因突變而使其無法正常組裝所致[1][2][3]。已知核糖體病變導致的疾病包括多數的先天性純紅細胞再生障礙性貧血英语Diamond–Blackfan anemia(DBA)[2]、某些肌肉萎縮症英语Muscle atrophy[4]X染色體偶連先天性角化不良症英语dyskeratosis congenita亞型[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]、某些骨髓增生異常症候群北美印第安兒童肝硬化英语North American Indian childhood cirrhosis(NAIC)[9]孤立性先天無脾症英语isolated congenital asplenia(ACAS)[9][10][11][12]Bowen-Conradi症候群英语Bowen–Conradi syndrome(BWCNS)[13][14][15][16]CHARGE聯合畸形ANE症候群[17],另外還有數種癌症可能為核糖體異常所致[18]。許多疾病的致病機理與核糖體異常激活p53途徑有關[19][20]

核糖體組裝

 
核糖體組裝的過程,每一步驟的異常都可能導致核糖體病變而致病

真核生物組裝核糖體的過程首先為在核仁中由RNA聚合酶I英语RNA polymerase I轉錄產生45S前核糖體RNA英语Preribosomal RNA(pre-rRNA),此RNA經剪切後可產生32S rRNA與30S rRNA,前者可再被剪切成28S rRNA5.8S rRNA[21][22],後者則可被剪切成18S rRNA[23],28S、5.8S與獨立由RNA聚合酶III轉錄產生的5S rRNA可與核糖體蛋白組合成60S核糖體亞基[24],18S rRNA則與核糖體蛋白組合成40S核糖体亚基,轉譯進行時兩者再進一步結合產生80S核糖體。此過程中各步驟的異常都可能影響核糖體組裝而導致核糖體病變。

列表

核糖體異常
名稱 染色體 基因型[25] 表型 突變蛋白質 異常步驟
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 與H/ACA snoRNA以及端粒酶RNA組分結合[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 粒線體RNA剪接
NAIC 16q22.1 OMIM 607456 OMIM 604901 CIRH1A英语CIRH1A NOL11的結合受影響[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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外部連結