biostudies-literatureFoged MMHHMIHHMI (HHMI)e2414187121https://www.ebi.ac.uk/biostudies/studies/S-EPMC11588129biostudies-literatureUnknown121(47)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 <i>N6AMT1</i> 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 <i>N6AMT1</i>, 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 leProceedings of the National Academy of Sciences of the United States of AmericaCytosolic <i>N6AMT1-</i>dependent translation supports mitochondrial RNA processing.PMC11588129DRG-2250-16Lisci MJourdain AAFoged MMMootha VKBoutguetait DZinshteyn BMunch CAllen GERecazens EChollet SfalseCytosolic <i>N6AMT1-</i>dependent translation supports mitochondrial RNA processing.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 <i>N6AMT1</i> 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 <i>N6AMT1</i>, 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 le2024-01-01T00:00:00Z2024 Nov2026-06-02T06:23:22.803Z2025-04-04T09:58:36.868ZS-EPMC115881293950384710.1073/pnas.2414187121