p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability.

p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability.
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DOI:
10.1093/nar/gks774
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发表时间:
2012-10
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:
Yagi M;Uchiumi T;Takazaki S;Okuno B;Nomura M;Yoshida S;Kanki T;Kang D

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p32是一种进化上保守且广泛表达的多功能蛋白。虽然p32存在于不同的细胞内和细胞外位点,但它主要定位于与线粒体转录因子A相关的类核附近的线粒体基质。然而,人们对其在矩阵中的作用知之甚少。在这里,我们通过产生p32基因敲除小鼠来确定p32的功能。p32缺陷小鼠表现出与胚胎严重发育缺陷相关的妊娠中期致死性。从p32基因敲除胚胎中分离的原代胚胎成纤维细胞表现出严重的线粒体呼吸链功能障碍,因为线粒体蛋白质合成严重受损。重组p32结合RNA,而不是DNA,内源性p32与体内所有线粒体信使RNA相互作用。p32的RNA结合能力与线粒体翻译密切相关。免疫共沉淀显示p32与线粒体的密切联系。我们建议,p32是所需的功能性线粒体形成线粒体内的蛋白质合成。
p32 is an evolutionarily conserved and ubiquitously expressed multifunctional protein. Although p32 exists at diverse intra and extracellular sites, it is predominantly localized to the mitochondrial matrix near the nucleoid associated with mitochondrial transcription factor A. Nonetheless, its function in the matrix is poorly understood. Here, we determined p32 function via generation of p32-knockout mice. p32-deficient mice exhibited mid-gestation lethality associated with a severe developmental defect of the embryo. Primary embryonic fibroblasts isolated from p32-knockout embryos showed severe dysfunction of the mitochondrial respiratory chain, because of severely impaired mitochondrial protein synthesis. Recombinant p32 binds RNA, not DNA, and endogenous p32 interacts with all mitochondrial messenger RNA species in vivo. The RNA-binding ability of p32 is well correlated with the mitochondrial translation. Co-immunoprecipitation revealed the close association of p32 with the mitoribosome. We propose that p32 is required for functional mitoribosome formation to synthesize proteins within mitochondria.
DOI: 10.1126/science.1175371
发表时间: 2009-08-14
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: Mann, Matthias
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发表时间: 1991-01-01
期刊: ANNUAL REVIEW OF CELL BIOLOGY
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通讯作者: CLAYTON, DA
DOI: 10.1093/nar/5.3.637
发表时间: 1978-01-01
影响因子: 14.9
作者:
GROHMANN, K;AMALRIC, F;ATTARDI, G
通讯作者: ATTARDI, G