Mitochondrial biogenesis relies on both the nuclear and mitochondrial genomes, and imbalance in their expression can lead to inborn errors of metabolism, inflammation, and aging. Here, we investigate N6AMT1, a nucleo-cytosolic methyltransferase that exhibits genetic codependency with mitochondria. We determine transcriptional and translational profiles of N6AMT1 and report that it is required for the cytosolic translation of TRMT10C (MRPP1) and PRORP (MRPP3), two subunits of the mitochondrial RNAse P enzyme. In the absence of N6AMT1 , or when its catalytic activity is abolished, RNA processing within mitochondria is impaired, leading to the accumulation of unprocessed and double-stranded RNA, thus preventing mitochondrial protein synthesis and oxidative phosphorylation, and leading to an immune response. Our work sheds light on the function of N6AMT1 in protein synthesis and highlights a cytosolic program required for proper mitochondrial biogenesis.

中文翻译：

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胞质 N6AMT1 依赖性翻译支持线粒体 RNA 加工


线粒体生物发生依赖于核基因组和线粒体基因组，它们表达的不平衡会导致先天性新陈代谢、炎症和衰老错误。在这里，我们研究了 N6AMT1，一种与线粒体表现出遗传依赖性的核胞质甲基转移酶。我们确定了 N6AMT1 的转录和翻译谱，并报告它是线粒体 RNAse P 酶的两个亚基 TRMT10C （MRPP1） 和 PRORP （MRPP3） 的胞质翻译所必需的。在没有 N6AMT1 的情况下，或者当其催化活性被消除时，线粒体内的 RNA 加工受损，导致未加工和双链 RNA 的积累，从而阻止线粒体蛋白合成和氧化磷酸化，并导致免疫反应。我们的工作阐明了 N6AMT1 在蛋白质合成中的功能，并强调了正确线粒体生物发生所需的胞质程序。