SRSF12 is a primate-specific splicing factor that induces a tissue-specific gene expression program.

Alternative splicing expands proteomic diversity and is tightly regulated by splicing factors, including the serine/arginine-rich (SR) protein family. Here, we analyze the poorly characterized protein SRSF12. Although SRSF12 is conserved across vertebrates, it is lowly expressed in most mammals, and we find that SRSF12 knockout mice do not display overt physiological or transcriptomic alterations. In contrast, SRSF12 is more highly expressed in primates, where it is predominantly transcribed in the testes, oocytes, and brain. SRSF12 colocalizes with other splicing components to nuclear speckles and interacts with splicing regulatory factors in cultured human cells. Strikingly, ectopic expression of SRSF12 in human cells induces widespread transcriptional changes, activating meiosis-, testis-, and brain-specific genes. SRSF12 overexpression also leads to mitotic arrest and cell death, phenotypes that require both its structured RNA recognition motif and intrinsically disordered arginine/serine-rich C-terminal domain. Together, our results suggest that SRSF12 has evolved primate-specific expression to regulate testis- and brain-specific genes.