Cytosolic N6AMT1-dependent translation supports mitochondrial RNA processing
成果类型：
Article
署名作者：
Foged, Mads M.; Recazens, Emeline; Chollet, Sylvain; Lisci, Miriam; Allen, George E.; Zinshteyn, Boris; Boutguetait, Doha; Muench, Christian; Mootha, Vamsi K.; Jourdain, Alexis A.
署名单位：
University of Lausanne; University of Geneva; Johns Hopkins University; Howard Hughes Medical Institute; Johns Hopkins University; Goethe University Frankfurt; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-11315
DOI：
10.1073/pnas.2414187121
发表日期：
2024-11-19
关键词：
methyltransferase 1 n6amt1
gene-expression
release factors
hemk2 protein
dna
target
identification
involvement
granules
adenine
摘要：
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.