Department of Immunobiology, University of Lausanne, Epalinges 1066, Switzerland.
Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva 4 1211, Switzerland.
Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2414187121. doi: 10.1073/pnas.2414187121. Epub 2024 Nov 6.
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 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 , 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 in protein synthesis and highlights a cytosolic program required for proper mitochondrial biogenesis.
线粒体生物发生依赖于核基因组和线粒体基因组，它们的表达失衡可导致先天性代谢错误、炎症和衰老。在这里，我们研究了 N6AMT1，一种具有核质依赖性的核质甲基转移酶。我们确定了 和 的转录和翻译谱，并报告它是细胞质翻译 TRMT10C（MRPP1）和 PRORP（MRPP3）所必需的，这两种酶是线粒体 RNAse P 酶的两个亚基。在没有 或其催化活性被废除的情况下，线粒体内部的 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质合成和氧化磷酸化，并导致免疫反应。我们的工作阐明了 在蛋白质合成中的功能，并强调了适当的线粒体生物发生所需的细胞质程序。
