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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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SRSF12 is a primate-specific splicing factor that induces a tissue-specific gene expression program.

Jimmy Ly1,2, Sarah L Cady1, Ekaterina Khalizeva1,2

  • 1Whitehead Institute for Biomedical Research, Cambridge, United States.

Biorxiv : the Preprint Server for Biology
|August 8, 2025
PubMed
Summary
This summary is machine-generated.

The serine/arginine-rich splicing factor 12 (SRSF12) protein is primate-specific and regulates key genes in the brain and testes. Its overexpression causes cell cycle arrest and death, highlighting its crucial role.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Alternative splicing generates proteomic diversity, regulated by splicing factors like serine/arginine-rich (SR) proteins.
  • The splicing factor SRSF12 is conserved but poorly characterized, with limited expression in most mammals.

Purpose of the Study:

  • To investigate the function and expression patterns of the splicing factor SRSF12.
  • To determine the role of SRSF12 in primate-specific gene regulation and cellular processes.

Main Methods:

  • Analysis of SRSF12 expression in various species and tissues.
  • Splicing factor interaction studies in cultured human cells.
  • Phenotypic analysis of SRSF12 knockout mice.
  • Ectopic SRSF12 expression studies in human cells.

Main Results:

  • SRSF12 knockout mice showed no significant physiological or transcriptomic changes.
  • SRSF12 is highly expressed in primate testes, oocytes, and brain, co-localizing with splicing machinery.
  • Ectopic SRSF12 expression induced primate-specific gene activation (meiosis, testis, brain) and caused mitotic arrest and cell death.

Conclusions:

  • SRSF12 exhibits primate-specific expression patterns, suggesting an evolved regulatory role.
  • The RNA recognition motif and C-terminal domain of SRSF12 are essential for its observed cellular effects.
  • SRSF12 plays a critical role in regulating testis- and brain-specific gene expression in primates.