SRSF1 is crucial for male meiosis through alternative splicing during homologous pairing and synapsis in mice [RNA-seq]
Homologous pairing and synapsis are essential in meiotic prophase I during spermatogenesis. However, the underlying mechanisms of how alternative splicing (AS) functions in homologous pairing and synapsis remain largely unclear. We reveal that SRSF1 is essential for gene expression and AS in homologous pairing and synapsis. Conditional knockout (cKO) of Srsf1 in mouse germ cells impaired homologous pairing and synapsis, leading to non-obstructive azoospermia (NOA). SRSF1 was required for initial homology recognition, telomere-led chromosome movement, and synaptonemal complex (SC) assembly. Moreover, SRSF1 interacted with TRA2B and U2AF2, directly binding and regulating the expression of Dmc1, Sycp1, Sun1, and Majin via AS to implement homologous pairing and synapsis during the meiotic prophase I program. Altogether, our data reveal the critical role of an SRSF1-mediated post-transcriptional regulatory mechanism in homologous pairing and synapsis during meiotic prophase I, providing a framework for elucidating the molecular mechanisms underlying the post-transcriptional network of male meiosis. Overall design: STRA8+ cell suspensions were isolated and prepared from mouse testes. Total RNA was extracted from STRA8+ cells.