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 poorly expressed in most mammals, and we find that SRSF12 knockouts in mice do not result in overt physiological or transcriptomic alterations. In contrast, SRSF12 is more highly expressed in primates where it is predominantly expressed during meiosis and in the brain. SRSF12 localizes to splicing speckles in cultured human cells and interacts with the core splicing factors. Strikingly, ectopic expression of SRSF12 in human cells induces widespread transcriptional changes, activating testis- and brain-specific gene expression programs. 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. Overall design: Biological replicates for RNA-sequencing were defined as replicate doxycycline inductions of GFP transgenes, n = 3. Biological replicates for animal work represent different animals, n = 2.