1. Biochemistry and Chemical Biology
  2. Cell Biology

YTHDC1 Mediates Nuclear Export of N6-methyladenosine Methylated mRNAs

  1. Ian A Roundtree
  2. Guan-Zheng Luo
  3. Zijie Zhang
  4. Xiao Wang
  5. Tao Zhou
  6. Yiquang Cui
  7. Jiahao Sha
  8. Xingxu Huang
  9. Laura Guerrero
  10. Phil Xie
  11. Emily He
  12. Bin Shen  Is a corresponding author
  13. Chuan He  Is a corresponding author
  1. University of Chicago, United States
  2. ShanghaiTech University, China
  3. Nanjing Medical University, China
  4. The University of Chicago, United States
https://doi.org/10.7554/eLife.31311
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  1. Ian A Roundtree
  2. Guan-Zheng Luo
  3. Zijie Zhang
  4. Xiao Wang
  5. Tao Zhou
  6. Yiquang Cui
  7. Jiahao Sha
  8. Xingxu Huang
  9. Laura Guerrero
  10. Phil Xie
  11. Emily He
  12. Bin Shen
  13. Chuan He
(2017)
YTHDC1 Mediates Nuclear Export of N6-methyladenosine Methylated mRNAs
eLife 6:e31311.
https://doi.org/10.7554/eLife.31311
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Abstract

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and plays critical roles in RNA biology. The function of this modification is mediated by m6A-selective 'reader' proteins of the YTH family, which incorporate m6A-modified mRNAs into pathways of RNA metabolism. Here, we show that the m6A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells. Knockdown of YTHDC1 results in an extended residence time for nuclear m6A-containing mRNA, with an accumulation of transcripts in the nucleus and accompanying depletion within the cytoplasm. YTHDC1 interacts with the splicing factor and nuclear export adaptor protein SRSF3, and facilitates RNA binding to both SRSF3 and NXF1. This role for YTHDC1 expands the potential utility of chemical modification of mRNA, and supports an emerging paradigm of m6A as a distinct biochemical entity for selective processing and metabolism of mammalian mRNAs.

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Author details

  1. Ian A Roundtree

    Department of Chemistry, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Guan-Zheng Luo

    Department of Chemistry, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Zijie Zhang

    Department of Chemistry, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Xiao Wang

    Department of Chemistry, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Tao Zhou

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Yiquang Cui

    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Jiahao Sha

    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Xingxu Huang

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  9. Laura Guerrero

    Department of Chemistry, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Phil Xie

    Department of Chemistry, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Emily He

    Department of Chemistry, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. Bin Shen

    State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
    For correspondence
    binshen@njmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

  13. Chuan He

    Department of Chemistry, The University of Chicago, Chicago, United States
    For correspondence
    chuanhe@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4319-7424

Funding

National Institute of General Medical Sciences (F30GM117646)

  • Ian A Roundtree

Howard Hughes Medical Institute

  • Ian A Roundtree
  • Guan-Zheng Luo
  • Zijie Zhang
  • Xiao Wang
  • Chuan He

National Science Foundation (CHE-1048528)

  • Ian A Roundtree
  • Guan-Zheng Luo
  • Zijie Zhang
  • Xiao Wang
  • Laura Guerrero
  • Phil Xie
  • Emily He
  • Chuan He

National Institute of General Medical Sciences (HG008688)

  • Chuan He

National Institute of General Medical Sciences (GM113194)

  • Chuan He

National Natural Science Foundation of China (31171377)

  • Xingxu Huang

National Natural Science Foundation of China (31471400)

  • Xingxu Huang

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

Copyright

© 2017, Roundtree 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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  1. Ian A Roundtree
  2. Guan-Zheng Luo
  3. Zijie Zhang
  4. Xiao Wang
  5. Tao Zhou
  6. Yiquang Cui
  7. Jiahao Sha
  8. Xingxu Huang
  9. Laura Guerrero
  10. Phil Xie
  11. Emily He
  12. Bin Shen
  13. Chuan He
(2017)
YTHDC1 Mediates Nuclear Export of N6-methyladenosine Methylated mRNAs
eLife 6:e31311.
https://doi.org/10.7554/eLife.31311

Share this article

https://doi.org/10.7554/eLife.31311

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