Regulation of mitochondrion-associated cytosolic ribosomes by mammalian mitochondrial ribonuclease T2 (RNASET2).
Regulation of mitochondrion-associated cytosolic ribosomes by mammalian mitochondrial ribonuclease T2 (RNASET2).
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DOI：
10.1074/jbc.ra118.005433
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发表时间：
2018-12-21
期刊：
影响因子：
--
通讯作者：
Wang G
中科院分区：
文献类型：
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作者：
Huang J;Liu P;Wang G
线粒体蛋白质在线粒体基因组和核基因组中编码。这两个线粒体基因库的表达水平是共同调节和同步的。核编码的氧化磷酸化（OXPHOS）亚基的输入和组装通过接合线粒体核糖体来影响线粒体基质中的蛋白质合成。然而，线粒体外部的核糖体如何受到线粒体的调节，仍然是未被探索的。在这里，使用一系列的生化检测和基因敲低和过度表达HEK293或小鼠细胞，我们表明，与线粒体外膜相关的胞质核糖体RNA有非常不同的衰减模式，从内质网相关和非相关的胞质核糖体RNA。线粒体膜间间隙RNA酶T2（RNASET 2），其先前已显示降解线粒体RNA，也负责选择性降解外膜上的胞质rRNA。我们注意到，降解活动也对rRNA的核转录产生积极影响，表明存在补偿反馈机制，并影响线粒体内外的蛋白质翻译。这些发现为哺乳动物细胞线粒体内外的基因表达程序的共同调节建立了一种机制。
Mitochondrial proteins are encoded in both mitochondrial and nuclear genomes. The expression levels of these two pools of mitochondrial genes are co-regulated and synchronized. Import and assembly of the nucleus-encoded oxidative phosphorylation (OXPHOS) subunits affect protein synthesis in the mitochondrial matrix by engaging the mitochondrial ribosomes. How the ribosomes at the outside of mitochondria are regulated by mitochondria, however, remains mostly unexplored. Here, using an array of biochemical assays and genetic knockdown and overexpression in HEK293 or mouse cells, we show that cytosolic rRNAs that are associated with the mitochondrial outer membrane have very different decay patterns from those of both endoplasmic reticulum–associated and –nonassociated cytosolic rRNAs. Mitochondrial intermembrane space RNase T2 (RNASET2), which has been previously shown to degrade mitochondrial RNAs, is also responsible for selective degradation of the cytosolic rRNAs on the outer membrane. We noted that the degradation activity also has a positive effect on nuclear transcription of rRNAs, suggesting a compensatory feedback mechanism, and affects protein translations in and out of mitochondria. These findings establish a mechanism for the co-regulation of gene expression programs inside and outside of mitochondria in mammalian cells.