IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms15134.html
   My bibliography  Save this article

Intron retention is regulated by altered MeCP2-mediated splicing factor recruitment

Author

Listed:
  • Justin J. -L. Wong

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Gene Regulation in Cancer Laboratory, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney)

  • Dadi Gao

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney
    Bioinformatics Laboratory, Centenary Institute, University of Sydney)

  • Trung V. Nguyen

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Gene Regulation in Cancer Laboratory, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney)

  • Chau-To Kwok

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Gene Regulation in Cancer Laboratory, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney)

  • Michelle van Geldermalsen

    (Sydney Medical School, University of Sydney
    Origins of Cancer Program, Centenary Institute, University of Sydney)

  • Rob Middleton

    (Sydney Medical School, University of Sydney
    Bioinformatics Laboratory, Centenary Institute, University of Sydney)

  • Natalia Pinello

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Gene Regulation in Cancer Laboratory, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney)

  • Annora Thoeng

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney)

  • Rajini Nagarajah

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney)

  • Jeff Holst

    (Sydney Medical School, University of Sydney
    Origins of Cancer Program, Centenary Institute, University of Sydney)

  • William Ritchie

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney
    Bioinformatics Laboratory, Centenary Institute, University of Sydney
    CNRS, UMR 5203)

  • John E. J. Rasko

    (Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney
    Sydney Medical School, University of Sydney
    Cell and Molecular Therapies, Royal Prince Alfred Hospital)

Abstract

While intron retention (IR) is considered a widely conserved and distinct mechanism of gene expression control, its regulation is poorly understood. Here we show that DNA methylation directly regulates IR. We also find reduced occupancy of MeCP2 near the splice junctions of retained introns, mirroring the reduced DNA methylation at these sites. Accordingly, MeCP2 depletion in tissues and cells enhances IR. By analysing the MeCP2 interactome using mass spectrometry and RNA co-precipitation, we demonstrate that decreased MeCP2 binding near splice junctions facilitates IR via reduced recruitment of splicing factors, including Tra2b, and increased RNA polymerase II stalling. These results suggest an association between IR and a slower rate of transcription elongation, which reflects inefficient splicing factor recruitment. In summary, our results reinforce the interdependency between alternative splicing involving IR and epigenetic controls of gene expression.

Suggested Citation

  • Justin J. -L. Wong & Dadi Gao & Trung V. Nguyen & Chau-To Kwok & Michelle van Geldermalsen & Rob Middleton & Natalia Pinello & Annora Thoeng & Rajini Nagarajah & Jeff Holst & William Ritchie & John E., 2017. "Intron retention is regulated by altered MeCP2-mediated splicing factor recruitment," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15134
    DOI: 10.1038/ncomms15134
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms15134
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms15134?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15134. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.