ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation.

ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation.
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DOI:
10.1093/nar/gkq305
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发表时间:
2010-09
影响因子:
14.9
通讯作者:
Kang D
Kang D
中科院分区:
生物学2区
文献类型:
--
作者:
Uchiumi T;Ohgaki K;Yagi M;Aoki Y;Sakai A;Matsumoto S;Kang D

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ERAL 1是大肠杆菌Era蛋白的同源物,是具有RNA结合活性的保守GTP结合蛋白。原核Era的缺失抑制细胞分裂而不影响染色体分离。在此之前,我们利用免疫沉淀法分离了与线粒体转录因子A相关的ERAL 1蛋白。在这项研究中,我们分析了ERAL 1在哺乳动物细胞中的定位和功能。ERAL 1定位于线粒体基质中,与包括12S rRNA在内的线粒体蛋白质相关。siRNA敲低ERAL 1降低线粒体翻译,引起核糖体小亚基的重新分布和减少12S rRNA。ERAL1在人HeLa细胞中的敲除增加了线粒体超氧化物的产生,并轻微降低了线粒体膜电位。敲低抑制HeLa细胞的生长,并伴随凋亡细胞的积累。这些结果表明ERAL 1定位于线粒体核糖体的一个小亚基,在小核糖体的构成中起重要作用,并且还参与细胞活力。
ERAL1, a homologue of Era protein in Escherichia coli, is a member of conserved GTP-binding proteins with RNA-binding activity. Depletion of prokaryotic Era inhibits cell division without affecting chromosome segregation. Previously, we isolated ERAL1 protein as one of proteins which were associated with mitochondrial transcription factor A by using immunoprecipitation. In this study, we analysed the localization and function of ERAL1 in mammalian cells. ERAL1 was localized in mitochondrial matrix and associated with mitoribosomal proteins including the 12S rRNA. siRNA knockdown of ERAL1 decreased mitochondrial translation, caused redistribution of ribosomal small subunits and reduced 12S rRNA. The knockdown of ERAL1 in human HeLa cells elevated mitochondrial superoxide production and slightly decreased mitochondrial membrane potential. The knockdown inhibited the growth of HeLa cells with an accumulation of apoptotic cells. These results suggest that ERAL1 is localized in a small subunit of the mitochondrial ribosome, plays an important role in the small ribosomal constitution, and is also involved in cell viability.
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