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Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis
Myelination depends on timely, precise control of oligodendrocyte differentiation and myelinogenesis. Cholesterol is the most abundant component of myelin and essential for myelin membrane assembly in the central nervous system. However, the underlying mechanisms of precise control of cholesterol bi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139834/ https://www.ncbi.nlm.nih.gov/pubmed/33942715 http://dx.doi.org/10.7554/eLife.60467 |
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author | Zhou, Xin Shin, Seula He, Chenxi Zhang, Qiang Rasband, Matthew N Ren, Jiangong Dai, Congxin Zorrilla-Veloz, Rocío I Shingu, Takashi Yuan, Liang Wang, Yunfei Chen, Yiwen Lan, Fei Hu, Jian |
author_facet | Zhou, Xin Shin, Seula He, Chenxi Zhang, Qiang Rasband, Matthew N Ren, Jiangong Dai, Congxin Zorrilla-Veloz, Rocío I Shingu, Takashi Yuan, Liang Wang, Yunfei Chen, Yiwen Lan, Fei Hu, Jian |
author_sort | Zhou, Xin |
collection | PubMed |
description | Myelination depends on timely, precise control of oligodendrocyte differentiation and myelinogenesis. Cholesterol is the most abundant component of myelin and essential for myelin membrane assembly in the central nervous system. However, the underlying mechanisms of precise control of cholesterol biosynthesis in oligodendrocytes remain elusive. In the present study, we found that Qki depletion in neural stem cells or oligodendrocyte precursor cells in neonatal mice resulted in impaired cholesterol biosynthesis and defective myelinogenesis without compromising their differentiation into Aspa(+)Gstpi(+) myelinating oligodendrocytes. Mechanistically, Qki-5 functions as a co-activator of Srebp2 to control transcription of the genes involved in cholesterol biosynthesis in oligodendrocytes. Consequently, Qki depletion led to substantially reduced concentration of cholesterol in mouse brain, impairing proper myelin assembly. Our study demonstrated that Qki-Srebp2-controlled cholesterol biosynthesis is indispensable for myelinogenesis and highlights a novel function of Qki as a transcriptional co-activator beyond its canonical function as an RNA-binding protein. |
format | Online Article Text |
id | pubmed-8139834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-81398342021-05-24 Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis Zhou, Xin Shin, Seula He, Chenxi Zhang, Qiang Rasband, Matthew N Ren, Jiangong Dai, Congxin Zorrilla-Veloz, Rocío I Shingu, Takashi Yuan, Liang Wang, Yunfei Chen, Yiwen Lan, Fei Hu, Jian eLife Developmental Biology Myelination depends on timely, precise control of oligodendrocyte differentiation and myelinogenesis. Cholesterol is the most abundant component of myelin and essential for myelin membrane assembly in the central nervous system. However, the underlying mechanisms of precise control of cholesterol biosynthesis in oligodendrocytes remain elusive. In the present study, we found that Qki depletion in neural stem cells or oligodendrocyte precursor cells in neonatal mice resulted in impaired cholesterol biosynthesis and defective myelinogenesis without compromising their differentiation into Aspa(+)Gstpi(+) myelinating oligodendrocytes. Mechanistically, Qki-5 functions as a co-activator of Srebp2 to control transcription of the genes involved in cholesterol biosynthesis in oligodendrocytes. Consequently, Qki depletion led to substantially reduced concentration of cholesterol in mouse brain, impairing proper myelin assembly. Our study demonstrated that Qki-Srebp2-controlled cholesterol biosynthesis is indispensable for myelinogenesis and highlights a novel function of Qki as a transcriptional co-activator beyond its canonical function as an RNA-binding protein. eLife Sciences Publications, Ltd 2021-05-04 /pmc/articles/PMC8139834/ /pubmed/33942715 http://dx.doi.org/10.7554/eLife.60467 Text en © 2021, Zhou et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Zhou, Xin Shin, Seula He, Chenxi Zhang, Qiang Rasband, Matthew N Ren, Jiangong Dai, Congxin Zorrilla-Veloz, Rocío I Shingu, Takashi Yuan, Liang Wang, Yunfei Chen, Yiwen Lan, Fei Hu, Jian Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis |
title | Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis |
title_full | Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis |
title_fullStr | Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis |
title_full_unstemmed | Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis |
title_short | Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis |
title_sort | qki regulates myelinogenesis through srebp2-dependent cholesterol biosynthesis |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139834/ https://www.ncbi.nlm.nih.gov/pubmed/33942715 http://dx.doi.org/10.7554/eLife.60467 |
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