SRSF1 serves as a critical posttranscriptional regulator at the late stage of thymocyte development

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 TCR beta(hi)CD24(+)CD69(+) immature to TCR beta(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 Il-27ra 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.

Automated summary

This study reveals a crucial role of serine/arginine-rich splicing factor 1 (SRSF1) in regulating thymocyte maturation by controlling gene networks involved in differentiation, proliferation, apoptosis, and interferon signaling pathway. Deletion of SRSF1 results in severe defects in thymocyte development, affecting the maturation and migration of T cells in the thymus.