| First Author | Vogel KU | Year | 2016 |
| Journal | J Immunol | Volume | 197 |
| Issue | 7 | Pages | 2673-2685 |
| PubMed ID | 27566829 | Mgi Jnum | J:317871 |
| Mgi Id | MGI:6844206 | Doi | 10.4049/jimmunol.1600854 |
| Citation | Vogel KU, et al. (2016) The RNA-Binding Proteins Zfp36l1 and Zfp36l2 Enforce the Thymic beta-Selection Checkpoint by Limiting DNA Damage Response Signaling and Cell Cycle Progression. J Immunol 197(7):2673-2685 |
| abstractText | The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly to enforce the beta-selection checkpoint during thymopoiesis, yet their molecular targets remain largely unknown. In this study, we identify these targets on a genome-wide scale in primary mouse thymocytes and show that Zfp36l1/l2 regulate DNA damage response and cell cycle transcripts to ensure proper beta-selection. Double-negative 3 thymocytes lacking Zfp36l1/l2 share a gene expression profile with postselected double-negative 3b cells despite the absence of intracellular TCRbeta and reduced IL-7 signaling. Our findings show that in addition to controlling the timing of proliferation at beta-selection, posttranscriptional control by Zfp36l1/l2 limits DNA damage responses, which are known to promote thymocyte differentiation. Zfp36l1/l2 therefore act as posttranscriptional safeguards against chromosomal instability and replication stress by integrating pre-TCR and IL-7 signaling with DNA damage and cell cycle control. |
