ArticleNature communications2020
A translational program that suppresses metabolism to shield the genome.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- eIF5A coordinates the transcription and translation of its target genes.Cellular and molecular life sciences : CMLS · 2026Article
- Hypusination of the translation factor eIF5A regulates mitochondrial tRNA processing to promote prostate cancer aggressiveness.Nature communications · 2026Article
- Amyloid-bodies in the evolution of malignancies.PloS one · 2026Article
- Acidosis attenuates the hypoxic stabilization of HIF-1α by activating lysosomal degradation.The Journal of cell biology · 2025Article
- The Role of TPM3 in Protecting Cardiomyocyte from Hypoxia-Induced Injury via Cytoskeleton Stabilization.International journal of molecular sciences · 2024Article
- Current Strategies and Therapeutic Applications of Mesenchymal Stem Cell-Based Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Inhibition of protein translation under matrix-deprivation stress in breast cancer cells.Frontiers in medicine · 2023Article
- MATRIX platform to analyze translation machinery remodeling in glioblastoma cells.STAR protocols · 2022Article
- Global analyses of mRNA expression in human sensory neurons reveal eIF5A as a conserved target for inflammatory pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Difluoromethylornithine (DFMO) Enhances the Cytotoxicity of PARP Inhibition in Ovarian Cancer Cells.Medical sciences (Basel, Switzerland) · 2022Article
- Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus.Cells · 2021Review
- Proteomics reveal cap-dependent translation inhibitors remodel the translation machinery and translatome.Cell reports · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Translatome reprogramming is a primary determinant of protein levels during stimuli adaptation. This raises the question: what are the translatome remodelers that reprogram protein output to activate biochemical adaptations. Here, we identify a translational pathway that represses metabolism to safeguard genome integrity. A system-wide MATRIX survey identified the ancient eIF5A as a pH-regulated translation factor that responds to fermentation-induced acidosis. TMT-pulse-SILAC analysis identified several pH-dependent proteins, including the mTORC1 suppressor Tsc2 and the longevity regulator Sirt1. Sirt1 operates as a pH-sensor that deacetylates nuclear eIF5A during anaerobiosis, enabling the cytoplasmic export of eIF5A/Tsc2 mRNA complexes for translational engagement. Tsc2 induction inhibits mTORC1 to suppress cellular metabolism and prevent acidosis-induced DNA damage. Depletion of eIF5A or Tsc2 leads to metabolic re-initiation and proliferation, but at the expense of incurring substantial DNA damage. We suggest that eIF5A operates as a translatome remodeler that suppresses metabolism to shield the genome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.