Academic Journal
Disruption of pathways regulated by Integrator complex in Galloway–Mowat syndrome due to WDR73 mutations
| العنوان: | Disruption of pathways regulated by Integrator complex in Galloway–Mowat syndrome due to WDR73 mutations |
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| المؤلفون: | F. C. Tilley, C. Arrondel, C. Chhuon, M. Boisson, N. Cagnard, M. Parisot, G. Menara, N. Lefort, I. C. Guerrera, C. Bole-Feysot, A. Benmerah, C. Antignac, G. Mollet |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Several studies have reported WDR73 mutations to be causative of Galloway–Mowat syndrome, a rare disorder characterised by the association of neurological defects and renal-glomerular disease. In this study, we demonstrate interaction of WDR73 with the INTS9 and INTS11 components of Integrator, a large multiprotein complex with various roles in RNA metabolism and transcriptional control. We implicate WDR73 in two Integrator-regulated cellular pathways; namely, the processing of uridylate-rich small nuclear RNAs (UsnRNA), and mediating the transcriptional response to epidermal growth factor stimulation. We also show that WDR73 suppression leads to altered expression of genes encoding cell cycle regulatory proteins. Altogether, our results suggest that a range of cellular pathways are perturbed by WDR73 loss-of-function, and support the consensus that proper regulation of UsnRNA maturation, transcription initiation and cell cycle control are all critical in maintaining the health of post-mitotic cells such as glomerular podocytes and neurons, and preventing degenerative disease. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-021-84472-7 |
| URL الوصول: | https://doaj.org/article/167c8a987f01465c88c9cb66da245073 |
| رقم الانضمام: | edsdoj.167c8a987f01465c88c9cb66da245073 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-021-84472-7 |