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

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, Hidenori Ichijo, Taishin Akiyama, Tadashi Yamamoto

研究成果: ジャーナルへの寄稿学術誌査読

8 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号6169
ジャーナルNature communications
11
1
DOI
出版ステータス出版済み - 12月 2020
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

フィンガープリント

「The CCR4–NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル