ArticleCell reports2023
Nuclear translocation of an aminoacyl-tRNA synthetase may mediate a chronic "integrated stress response".
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 8 citations in OpenAlex.
- The TyrRS cascade: circadian gating of neuronal DNA repair and its collapse in aging.GeroScience · 2026Review
- Tyrosine Supplementation Rescues a Growth Defect in a HumanizedInternational journal of molecular sciences · 2026Article
- A metabolite-bridged complex between SerRS and SIRT2 couples NAD⁺ metabolism to translation control.Nature communications · 2026Article
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- Suppression rather than activation of the integrated stress response (GCN2-ATF4) pathway extends lifespan in the fly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- DARS expression in JAK2V617F-positive myeloproliferative neoplasms: immunohistochemical analysis and clinical associations.Annals of hematology · 2026Article
- Decoding human tRNA modifications and crosstalk by enhanced single-read analysis.Genome biology · 2026Article
- Proteomic and metabolomic insights into oxidative stress response activation in mouse embryos generated byHuman reproduction open · 2025Article
- Seryl-tRNA synthetase promotes translational readthrough by mRNA binding and involvement of the selenocysteine incorporation machinery.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Various stress conditions are signaled through phosphorylation of translation initiation factor eukaryotic initiation factor 2α (eIF2α) to inhibit global translation while selectively activating transcription factor ATF4 to aid cell survival and recovery. However, this integrated stress response is acute and cannot resolve lasting stress. Here, we report that tyrosyl-tRNA synthetase (TyrRS), a member of the aminoacyl-tRNA synthetase family that responds to diverse stress conditions through cytosol-nucleus translocation to activate stress-response genes, also inhibits global translation. However, it occurs at a later stage than eIF2α/ATF4 and mammalian target of rapamycin (mTOR) responses. Excluding TyrRS from the nucleus over-activates translation and increases apoptosis in cells under prolonged oxidative stress. Nuclear TyrRS transcriptionally represses translation genes by recruiting TRIM28 and/or NuRD complex. We propose that TyrRS, possibly along with other family members, can sense a variety of stress signals through intrinsic properties of this enzyme and strategically located nuclear localization signal and integrate them by nucleus translocation to effect protective responses against chronic stress.
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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.