RNA-seq data for: A conserved mito-cytoplasmic translational balance links two longevity pathways

Slowing down mRNA translation in either the cytoplasm or the mitochondria are both conserved longevity mechanisms. Here, we found a non-interventional natural correlation of mitochondrial and cytoplasmic ribosomal proteins when looking at mouse population genetics, suggesting a mito-cytoplasmic translational balance. Additionally, inhibiting mitochondrial translation in C. elegans in turn reduced cytoplasmic translation and repressed growth pathways while upregulating stress responses at both proteome and transcriptome levels. This coordinated repression of cytoplasmic translation is dependent on the atf-5/Atf4 transcription factor and is conserved in mammalian cells upon inhibiting mitochondrial translation pharmacologically with the antibiotic doxycycline. Lastly, extending this to a mammalian setting using doxycycline-treated germ-free mice, we found repressed cytoplasmic translation and ribosomal proteins in liver. These data demonstrate that inhibiting mitochondrial translation initiates a signaling cascade leading to coordinated repression of cytoplasmic translation, unlike previously described unidirectional cyto-to-mito translational communication in yeast, which can be targeted to promote healthy aging. In total 30 samples were sequenced: 18 were from C. elegans worms, 12 were from M. musculus mouse. Worm samples consisted of either (1) total RNA of whole worms, (2) polysomal RNA of whole worms, or (3) monosomal RNA of whole worms, performed in triplicate for both treatment (mrps-5 RNAi) and control (empty vector) worms. Mouse samples consisted of either (1) total RNA of liver or (2) polysomal RNA of liver, performed in triplicate for both treatment (doxycycline, 50mg/kg/d for two weeks) or control (amoxicillin, 50mg/kg/d for two weeks) in germ-free mice.