1. Developmental Biology
  2. Neuroscience
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Qki regulates myelinogenesis through Srebp2-dependent cholesterol biosynthesis

  1. Xin Zhou
  2. Seula Shin
  3. Chenxi He
  4. Qiang Zhang
  5. Matthew N Rasband
  6. Jiangong Ren
  7. Congxin Dai
  8. Rocío I Zorrilla-Veloz
  9. Takashi Shingu
  10. Liang Yuan
  11. Yunfei Wang
  12. Yiwen Chen
  13. Fei Lan
  14. Jian Hu  Is a corresponding author
  1. MD Anderson Cancer Center, United States
  2. Fudan University, China
  3. Baylor College of Medicine, United States
  4. Chinese Academy of Medical Sciences and Peking Union Medical College, China
  5. Tufts University, United States
Research Article
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Cite this article as: eLife 2021;10:e60467 doi: 10.7554/eLife.60467

Abstract

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 the 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.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE145116, GSE145117 and GSE144756

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Xin Zhou

    Department of Cancer Biology, MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Seula Shin

    Department of Cancer Biology, MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Chenxi He

    Liver Cancer Institute, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Qiang Zhang

    Department of Cancer Biology, MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Matthew N Rasband

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8184-2477
  6. Jiangong Ren

    Department of Cancer Biology, MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Congxin Dai

    Department of Neurosurgery, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Rocío I Zorrilla-Veloz

    Department of Cancer Biology, MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Takashi Shingu

    Department of Cancer Biology, MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Liang Yuan

    Graduate School of Biomedical Sciences, Tufts University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Yunfei Wang

    Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Yiwen Chen

    Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Fei Lan

    Liver Cancer Institute, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Jian Hu

    Department of Cancer Biology, MD Anderson Cancer Center, Houston, United States
    For correspondence
    JHu3@mdanderson.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9760-2013

Funding

NCI (R37CA214800)

  • Jian Hu

MD Anderson Cancer Center (startup)

  • Jian Hu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All mouse experiments were conducted in accordance with protocols approved by the MD Anderson Institutional Animal Care and Use Committee. (IACUC Study #00001392-RN01)

Reviewing Editor

  1. Jian Xu, University of Texas Southwestern Medical Center, United States

Publication history

  1. Received: June 26, 2020
  2. Accepted: May 1, 2021
  3. Accepted Manuscript published: May 4, 2021 (version 1)

Copyright

© 2021, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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