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 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 co-localizes with other splicing components to nuclear speckles and interacts with core splicing 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.

• Publication year

  2025

• Venue

  bioRxiv

• Publication date

  2025-07-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1101/2025.07.25.666902PMID 41060796PMCID 12330525
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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