IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-19975-4.html
   My bibliography  Save this article

The CCR4–NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression

Author

Listed:
  • Taku Ito-Kureha

    (Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University)

  • Takahisa Miyao

    (Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences)

  • Saori Nishijima

    (Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University)

  • Toru Suzuki

    (Laboratory for Immunogenetics, RIKEN Center for Integrative Medical Sciences)

  • Shin-ichi Koizumi

    (Immune Signal Unit, Okinawa Institute of Science and Technology Graduate University)

  • Alejandro Villar-Briones

    (Instrumental Analysis Section, Research Support Division, Okinawa Institute of Science and Technology Graduate University)

  • Akinori Takahashi

    (Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University)

  • Nobuko Akiyama

    (Laboratory for Immunogenetics, RIKEN Center for Integrative Medical Sciences)

  • Masahiro Morita

    (Department of Molecular Medicine and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio)

  • Isao Naguro

    (Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Hiroki Ishikawa

    (Immune Signal Unit, Okinawa Institute of Science and Technology Graduate University)

  • Hidenori Ichijo

    (Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Taishin Akiyama

    (Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences)

  • Tadashi Yamamoto

    (Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University
    Laboratory for Immunogenetics, RIKEN Center for Integrative Medical Sciences)

Abstract

A repertoire of T cells with diverse antigen receptors is selected in the thymus. However, detailed mechanisms underlying this thymic positive selection are not clear. Here we show that the CCR4-NOT complex limits expression of specific genes through deadenylation of mRNA poly(A) tails, enabling positive selection. Specifically, the CCR4-NOT complex is up-regulated in thymocytes before initiation of positive selection, where in turn, it inhibits up-regulation of pro-apoptotic Bbc3 and Dab2ip. Elimination of the CCR4-NOT complex permits up-regulation of Bbc3 during a later stage of positive selection, inducing thymocyte apoptosis. In addition, CCR4-NOT elimination up-regulates Dab2ip at an early stage of positive selection. Thus, CCR4-NOT might control thymocyte survival during two-distinct stages of positive selection by suppressing expression levels of pro-apoptotic molecules. Taken together, we propose a link between CCR4-NOT-mediated mRNA decay and T cell selection in the thymus.

Suggested Citation

  • Taku Ito-Kureha & Takahisa Miyao & Saori Nishijima & Toru Suzuki & Shin-ichi Koizumi & Alejandro Villar-Briones & Akinori Takahashi & Nobuko Akiyama & Masahiro Morita & Isao Naguro & Hiroki Ishikawa &, 2020. "The CCR4–NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19975-4
    DOI: 10.1038/s41467-020-19975-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-19975-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-19975-4?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:11:y:2020:i:1:d:10.1038_s41467-020-19975-4. 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.