| First Author | Ito-Kureha T | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 6169 |
| PubMed ID | 33268794 | Mgi Jnum | J:300963 |
| Mgi Id | MGI:6504537 | Doi | 10.1038/s41467-020-19975-4 |
| Citation | Ito-Kureha T, et al. (2020) The CCR4-NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression. Nat Commun 11(1):6169 |
| abstractText | 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. |
