| First Author | Qi Z | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 16 | PubMed ID | 33863728 |
| Mgi Jnum | J:314927 | Mgi Id | MGI:6809705 |
| Doi | 10.1126/sciadv.abf0753 | Citation | Qi Z, et al. (2021) SRSF1 serves as a critical posttranscriptional regulator at the late stage of thymocyte development. Sci Adv 7(16) |
| abstractText | The underlying mechanisms of thymocyte maturation remain largely unknown. Here, we report that serine/arginine-rich splicing factor 1 (SRSF1) intrinsically regulates the late stage of thymocyte development. Conditional deletion of SRSF1 resulted in severe defects in maintenance of late thymocyte survival and a blockade of the transition of TCRbeta(hi)CD24(+)CD69(+) immature to TCRbeta(hi)CD24(-)CD69(-) mature thymocytes, corresponding to a notable reduction of recent thymic emigrants and diminished periphery T cell pool. Mechanistically, SRSF1 regulates the gene networks involved in thymocyte differentiation, proliferation, apoptosis, and type I interferon signaling pathway to safeguard T cell intrathymic maturation. In particular, SRSF1 directly binds and regulates Irf7 and Il27ra expression via alternative splicing in response to type I interferon signaling. Moreover, forced expression of interferon regulatory factor 7 rectifies the defects in SRSF1-deficient thymocyte maturation via restoring expression of type I interferon-related genes. Thus, our work provides new insight on SRSF1-mediated posttranscriptional regulatory mechanism of thymocyte development. |
