GTPBP1 resolves paused ribosomes to maintain neuronal homeostasis
| العنوان: | GTPBP1 resolves paused ribosomes to maintain neuronal homeostasis |
|---|---|
| المؤلفون: | Tianda Deng, Jeffrey H. Chuang, Markus Terrey, Alana L Gibson, Ryuta Ishimura, Susan L. Ackerman, Scott I Adamson |
| المصدر: | eLife, Vol 9 (2020) eLife |
| بيانات النشر: | eScholarship, University of California, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, retina, Mouse, hippocampus, GTPase, Ribosome, neuroscience, Mice, 0302 clinical medicine, Biology (General), Neurons, Chemistry, General Neuroscience, Neurodegeneration, Neurodegenerative Diseases, General Medicine, Chromosomes and Gene Expression, Anti-Bacterial Agents, Cell biology, Neurological, Transfer RNA, Medicine, Neuron death, Signal Transduction, chromosomes, ribosome stalling, cerebellum, QH301-705.5, Knockout, 1.1 Normal biological development and functioning, Science, tRNA-Arg-TCT-4-1, Mechanistic Target of Rapamycin Complex 1, Neuroprotection, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Underpinning research, Genetics, medicine, Animals, Integrated stress response, mouse, Monomeric GTP-Binding Proteins, Sirolimus, General Immunology and Microbiology, Neurosciences, medicine.disease, Transfer, 030104 developmental biology, Gene Expression Regulation, gene expression, RNA, Translational elongation, Biochemistry and Cell Biology, Research Advance, Ribosomes, 030217 neurology & neurosurgery, granule cells, Neuroscience |
| الوصف: | Ribosome-associated quality control pathways respond to defects in translational elongation to recycle arrested ribosomes and degrade aberrant polypeptides and mRNAs. Loss of a tRNA gene leads to ribosomal pausing that is resolved by the translational GTPase GTPBP2, and in its absence causes neuron death. Here, we show that loss of the homologous protein GTPBP1 during tRNA deficiency in the mouse brain also leads to codon-specific ribosome pausing and neurodegeneration, suggesting that these non-redundant GTPases function in the same pathway to mitigate ribosome pausing. As observed in Gtpbp2-/- mice (Ishimura et al., 2016), GCN2-mediated activation of the integrated stress response (ISR) was apparent in the Gtpbp1-/- brain. We observed decreased mTORC1 signaling which increased neuronal death, whereas ISR activation was neuroprotective. Our data demonstrate that GTPBP1 functions as an important quality control mechanism during translation elongation and suggest that translational signaling pathways intricately interact to regulate neuronal homeostasis during defective elongation. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2e01fe89949883aeb8c99964d9ef333 https://escholarship.org/uc/item/089743rs |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f2e01fe89949883aeb8c99964d9ef333 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |