Cytosolic N6AMT1- dependent translation supports mitochondrial RNA processing.

Autor:	Foged MM; Department of Immunobiology, University of Lausanne, Epalinges 1066, Switzerland., Recazens E; Department of Immunobiology, University of Lausanne, Epalinges 1066, Switzerland., Chollet S; Department of Immunobiology, University of Lausanne, Epalinges 1066, Switzerland., Lisci M; Department of Immunobiology, University of Lausanne, Epalinges 1066, Switzerland., Allen GE; Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva 4 1211, Switzerland., Zinshteyn B; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205.; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205., Boutguetait D; Institute of Molecular Systems Medicine, Faculty of Medicine, Goethe University Frankfurt, Frankfurt am Main 60590, Germany., Münch C; Institute of Molecular Systems Medicine, Faculty of Medicine, Goethe University Frankfurt, Frankfurt am Main 60590, Germany., Mootha VK; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142.; HHMI, Massachusetts General Hospital Boston, MA 02114.; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114.; Department of Systems Biology, Harvard Medical School, Boston, MA 02115., Jourdain AA; Department of Immunobiology, University of Lausanne, Epalinges 1066, Switzerland.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Nov 19; Vol. 121 (47), pp. e2414187121. Date of Electronic Publication: 2024 Nov 06.
DOI:	10.1073/pnas.2414187121
Abstrakt:	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. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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