Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy
| العنوان: | Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy |
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| المؤلفون: | Natalia L. Kononenko, Susanne Motameny, Miriam Peters, Maximilian P. Thelen, Brunhilde Wirth, Inês do Carmo G. Gonçalves, Janine Altmüller, Wiebke A. Rehorst, Hyun Ju Lee, Darius Ebrahimi-Fakhari, Min Jeong Kye, Johanna Brecht, David Vilchez, Mustafa Sahin, Laura Torres-Benito |
| المصدر: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) |
| بيانات النشر: | Nature Publishing Group UK, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Ribonuclease III, 0301 basic medicine, lcsh:Medicine, Biology, Article, Muscular Atrophy, Spinal, Microprocessor complex, Mice, 03 medical and health sciences, microRNA, Autophagy, medicine, Animals, Premovement neuronal activity, lcsh:Science, Author Correction, Drosha, Mice, Knockout, Motor Neurons, Multidisciplinary, lcsh:R, Spinal muscular atrophy, Motor neuron, medicine.disease, SMA, Survival of Motor Neuron 1 Protein, Cell biology, Survival of Motor Neuron 2 Protein, Disease Models, Animal, MicroRNAs, Phenotype, 030104 developmental biology, medicine.anatomical_structure, nervous system, lcsh:Q, Subcellular Fractions |
| الوصف: | Dysregulated miRNA expression and mutation of genes involved in miRNA biogenesis have been reported in motor neuron diseases including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Therefore, identifying molecular mechanisms governing miRNA expression is important to understand these diseases. Here, we report that expression of DROSHA, which is a critical enzyme in the microprocessor complex and essential for miRNA biogenesis, is reduced in motor neurons from an SMA mouse model. We show that DROSHA is degraded by neuronal activity induced autophagy machinery, which is also dysregulated in SMA. Blocking neuronal activity or the autophagy-lysosome pathway restores DROSHA levels in SMA motor neurons. Moreover, reducing DROSHA levels enhances axonal growth. As impaired axonal growth is a well described phenotype of SMA motor neurons, these data suggest that DROSHA reduction by autophagy may mitigate the phenotype of SMA. In summary, these findings suggest that autophagy regulates RNA metabolism and neuronal growth via the DROSHA/miRNA pathway and this pathway is dysregulated in SMA. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d3bc0d9aa4cb320ee1fdc7ee157b0dfTest http://europepmc.org/articles/PMC5962575Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6d3bc0d9aa4cb320ee1fdc7ee157b0df |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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