Methylglyoxal couples metabolic and translational control of Notch signalling in mammalian neural stem cells
| العنوان: | Methylglyoxal couples metabolic and translational control of Notch signalling in mammalian neural stem cells |
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| المؤلفون: | Emily M. Harvey, James Ellis, Guang Yang, David L. Kaplan, Rejitha Suraj, Lamees Mohammad, Guiqiong He, Hongrui Liu, Deivid C. Rodrigues, Sarah L. Erickson, Mengli Ren |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Translation, Cellular differentiation, Neurogenesis, Science, Notch signaling pathway, General Physics and Astronomy, Developmental neurogenesis, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, otorhinolaryngologic diseases, Animals, Humans, RNA, Messenger, Receptor, Notch1, lcsh:Science, 3' Untranslated Regions, Regulation of gene expression, RNA metabolism, Neural stem cells, Multidisciplinary, Three prime untranslated region, Methylglyoxal, HEK 293 cells, Brain, Gene Expression Regulation, Developmental, Glyceraldehyde-3-Phosphate Dehydrogenases, Translation (biology), Cell Differentiation, General Chemistry, Pyruvaldehyde, Neural progenitors, Neural stem cell, Cell biology, stomatognathic diseases, 030104 developmental biology, HEK293 Cells, chemistry, Protein Biosynthesis, Female, lcsh:Q, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | Gene regulation and metabolism are two fundamental processes that coordinate the self-renewal and differentiation of neural precursor cells (NPCs) in the developing mammalian brain. However, little is known about how metabolic signals instruct gene expression to control NPC homeostasis. Here, we show that methylglyoxal, a glycolytic intermediate metabolite, modulates Notch signalling to regulate NPC fate decision. We find that increased methylglyoxal suppresses the translation of Notch1 receptor mRNA in mouse and human NPCs, which is mediated by binding of the glycolytic enzyme GAPDH to an AU-rich region within Notch1 3ʹUTR. Interestingly, methylglyoxal inhibits the enzymatic activity of GAPDH and engages it as an RNA-binding protein to suppress Notch1 translation. Reducing GAPDH levels or restoring Notch signalling rescues methylglyoxal-induced NPC depletion and premature differentiation in the developing mouse cortex. Taken together, our data indicates that methylglyoxal couples the metabolic and translational control of Notch signalling to control NPC homeostasis. Gene regulation and metabolism co-ordinate self-renewal and differentiation of neural precursors (NPCs) in the developing brain. Here the authors show that methylglyoxal, a glycolytic intermediate metabolite, promotes GADPH-dependent translational repression of Notch1, thereby promoting NPC differentiation. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d999fed764488c2cc1ea39ddf4299f2 http://link.springer.com/article/10.1038/s41467-020-15941-2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8d999fed764488c2cc1ea39ddf4299f2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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