The Human Mitochondrial DEAD-Box Protein DDX28 Resides in RNA Granules and Functions in Mitoribosome Assembly.
The Human Mitochondrial DEAD-Box Protein DDX28 Resides in RNA Granules and Functions in Mitoribosome Assembly.
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DOI：
10.1016/j.celrep.2015.01.033
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发表时间：
2015-02-17
期刊：
影响因子：
8.8
通讯作者：
Barrientos A
中科院分区：
文献类型：
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作者：
Tu YT;Barrientos A
人类线粒体核糖体专门合成13种蛋白质，这些蛋白质是氧化磷酸化系统的基本组成部分。有丝分裂体生物发生的途径、该过程的区室化和所涉及的因素在很大程度上仍然未知。在这里，我们已经确定了死亡盒蛋白DDX 28作为一个RNA颗粒组成部分的线粒体大亚基（mt-LSU）的生物合成必不可少的。DDX 28与16 S rRNA和mt-LSU相互作用。HEK 293 T细胞中RNAi介导的DDX 28沉默不影响线粒体mRNA稳定性、16 S rRNA加工或修饰。然而，它导致16 S rRNA和mt-LSU蛋白水平降低，mt-LSU组装受损，线粒体蛋白合成深度减弱，从而组装氧化磷酸化复合物失败。我们的研究结果确定DDX 28在线粒体mt-LSU生物发生的早期阶段是必不可少的，这一过程主要发生在线粒体类核附近，在由RNA颗粒定义的隔室中。
Human mitochondrial ribosomes are specialized in the synthesis of 13 proteins, which are fundamental components of the oxidative phosphorylation system. The pathway of mitoribosome biogenesis, the compartmentalization of the process and factors involved remain largely unknown. Here, we have identified the DEAD box protein DDX28 as an RNA granule component essential for the biogenesis of the mitoribosome large subunit (mt-LSU). DDX28 interacts with the 16S rRNA and the mt-LSU. RNAi-mediated DDX28 silencing in HEK293T cells does not affect mitochondrial mRNA stability, 16S rRNA processing or modification. However, it leads to reduced levels of 16S rRNA and mt-LSU proteins, impaired mt-LSU assembly, deeply attenuated mitochondrial protein synthesis and consequent failure to assemble oxidative phosphorylation complexes. Our findings identify DDX28 as essential during the early stages of mitoribosome mt-LSU biogenesis, a process that mainly takes place near the mitochondrial nucleoids, in the compartment defined by the RNA granules.