CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins.
CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins.
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DOI：
10.1083/jcb.201403129
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发表时间：
2014-10-27
期刊：
影响因子：
--
通讯作者：
Rugarli EI
中科院分区：
文献类型：
--
作者：
Gao J;Schatton D;Martinelli P;Hansen H;Pla-Martin D;Barth E;Becker C;Altmueller J;Frommolt P;Sardiello M;Rugarli EI
CLUH是一种细胞溶质mRNA结合蛋白，其特异性结合编码线粒体蛋白的mRNA的子集，并可调节其定位翻译。线粒体功能需要两个基因组的协调，以实现蛋白质生物合成、有效的质量控制机制以及细胞器在细胞内的适当分布。目前还不清楚这些机制是如何整合的。Clu 1/CluA同源基因（CLUH）的丢失导致了线粒体网络的聚类，其机制未知。我们发现，CLUH是共同调节的基因编码线粒体蛋白质和基因参与核糖体的生物合成和翻译。我们的功能分析确定CLUH作为一种细胞溶质信使核糖核酸（RNA; mRNA）结合蛋白。RNA免疫沉淀实验和下一代测序表明，CLUH特异性结合编码线粒体蛋白的mRNA亚组。CLUH缺失降低了靶转录物翻译的蛋白质水平，并引起线粒体聚集。CLUH的一部分与酪氨酸化微管蛋白共定位，并且可以在线粒体附近检测到，这表明其在调节线粒体附近靶转录物的转运或翻译中发挥作用。我们的数据揭示了一种连接线粒体生物发生和分布的新机制。
CLUH is a cytosolic mRNA-binding protein that specifically binds a subset of mRNAs encoding mitochondrial proteins and may regulate their localized translation. Mitochondrial function requires coordination of two genomes for protein biogenesis, efficient quality control mechanisms, and appropriate distribution of the organelles within the cell. How these mechanisms are integrated is currently not understood. Loss of the Clu1/CluA homologue (CLUH) gene led to clustering of the mitochondrial network by an unknown mechanism. We find that CLUH is coregulated both with genes encoding mitochondrial proteins and with genes involved in ribosomal biogenesis and translation. Our functional analysis identifies CLUH as a cytosolic messenger ribonucleic acid (RNA; mRNA)–binding protein. RNA immunoprecipitation experiments followed by next-generation sequencing demonstrated that CLUH specifically binds a subset of mRNAs encoding mitochondrial proteins. CLUH depletion decreased the levels of proteins translated by target transcripts and caused mitochondrial clustering. A fraction of CLUH colocalizes with tyrosinated tubulin and can be detected close to mitochondria, suggesting a role in regulating transport or translation of target transcripts close to mitochondria. Our data unravel a novel mechanism linking mitochondrial biogenesis and distribution.
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影响因子：
4.3
作者：
Cox, Rachel T.;Spradling, Allan C.
通讯作者：
Spradling, Allan C.
影响因子：
7.2
作者：
Logan, DC;Scott, I;Tobin, AK
通讯作者：
Tobin, AK
DOI：
10.1073/pnas.0504400102
发表时间：
2005-07-19
影响因子：
11.1
作者：
Otto, H;Conz, C;Rospert, S
通讯作者：
Rospert, S
影响因子：
5.3
作者：
Koppen, Mirko;Metodiev, Metodi D.;Langer, Thomas
通讯作者：
Langer, Thomas
影响因子：
64.8
作者：
Clark, Ira E.;Dodson, Mark W.;Guo, Ming
通讯作者：
Guo, Ming