Cytosolic <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 leading to an immune response. Our work sheds light on the function of <i>N6AMT1</i> in protein synthesis and highlights a cytosolic program required for proper mitochondrial biogenesis.
Authors
- George Edward Allen (ORCID: https://orcid.org/0000-0002-1529-9928)
- Christian Münch (ORCID: https://orcid.org/0000-0003-3832-090X)
- Boris Zinshteyn (ORCID: https://orcid.org/0000-0003-0103-3501)
- Emeline Recazens (ORCID: https://orcid.org/0000-0003-3800-7411)
- Alexis A. Jourdain (ORCID: https://orcid.org/0000-0001-5321-6938)
- Mads Møller Foged (ORCID: https://orcid.org/0000-0003-2225-6114)
- Vamsi Krishna Mootha (ORCID: https://orcid.org/0000-0001-9924-642X)
- Miriam Lisci (ORCID: https://orcid.org/0000-0002-8627-4154)
- Doha Boutguetait
- Sylvain Chollet (ORCID: https://orcid.org/0009-0008-7769-844X)
Institutions
- Broad Institute (US)
- Goethe University Frankfurt (DE)
- University of Geneva (CH)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Massachusetts General Hospital (US)
- Center for Systems Biology (US)
- Massachusetts Institute of Technology (US)
- University of Lausanne (CH)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-11-06
- DOI
- https://doi.org/10.1073/pnas.2414187121
- Citations
- 8
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- National Science Foundation
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation
- Johns Hopkins University
- Université de Lausanne