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Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation

التفاصيل البيبلوغرافية
العنوان: Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation
المؤلفون: Ryuta Ishimura, Gabor Nagy, Ivan Dotu, Jeffrey H Chuang, Susan L Ackerman
المصدر: eLife, Vol 5 (2016)
بيانات النشر: eLife Sciences Publications Ltd, 2016.
سنة النشر: 2016
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: translation elongation, neurodegeneration, translation initiation, Medicine, Science, Biology (General), QH301-705.5
الوصف: Ribosome stalling during translation has recently been shown to cause neurodegeneration, yet the signaling pathways triggered by stalled elongation complexes are unknown. To investigate these pathways we analyzed the brain of C57BL/6J-Gtpbp2nmf205-/- mice in which neuronal elongation complexes are stalled at AGA codons due to deficiencies in a tRNAArgUCU tRNA and GTPBP2, a mammalian ribosome rescue factor. Increased levels of phosphorylation of eIF2α (Ser51) were detected prior to neurodegeneration in these mice and transcriptome analysis demonstrated activation of ATF4, a key transcription factor in the integrated stress response (ISR) pathway. Genetic experiments showed that this pathway was activated by the eIF2α kinase, GCN2, in an apparent deacylated tRNA-independent fashion. Further we found that the ISR attenuates neurodegeneration in C57BL/6J-Gtpbp2nmf205-/- mice, underscoring the importance of cellular and stress context on the outcome of activation of this pathway. These results demonstrate the critical interplay between translation elongation and initiation in regulating neuron survival during cellular stress.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/14295; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.14295
URL الوصول: https://doaj.org/article/4e33e8f16d1c4cf9ad15a0bfcbf9450b
رقم الأكسشن: edsdoj.4e33e8f16d1c4cf9ad15a0bfcbf9450b
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.14295