SRSF1 serves as a critical posttranscriptional regulator at the late stage of thymocyte development.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33863728.
- Also identified by DOI 10.1126/sciadv.abf0753 and PMC identifier 8051871.
- Licence recorded as CC BY-NC.
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Abstract
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 TCRβ<sup>hi</sup>CD24<sup>+</sup>CD69<sup>+</sup> immature to TCRβ<sup>hi</sup>CD24<sup>-</sup>CD69<sup>-</sup> 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 <i>Irf7</i> and <i>Il27ra</i> 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.