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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, Sofia Haug1

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA 02142.

Molecular Biology of the Cell
|October 8, 2025
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Summary

The splicing factor SRSF12 is highly expressed in primates, particularly in the brain and testes. Its overexpression in human cells activates specific genes and causes cell cycle arrest, suggesting a primate-specific role in gene regulation.

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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.
  • SRSF12 is a poorly characterized member of the SR protein family, conserved across vertebrates but with low expression in most mammals.

Purpose of the Study:

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

Main Methods:

  • Analysis of SRSF12 expression in different species and tissues.
  • SRSF12 knockout mouse model studies.
  • Co-localization and interaction studies in cultured human cells.
  • Ectopic SRSF12 expression experiments to assess transcriptional and cellular effects.

Main Results:

  • SRSF12 knockout mice showed no significant physiological or transcriptomic changes.
  • SRSF12 exhibits higher expression in primates, especially in testes, oocytes, and brain.
  • Ectopic SRSF12 expression in human cells induced testis- and brain-specific gene activation, mitotic arrest, and cell death.
  • Phenotypes required both RNA recognition motif and C-terminal domain of SRSF12.

Conclusions:

  • SRSF12 has evolved primate-specific expression patterns.
  • SRSF12 plays a role in regulating primate-specific genes, particularly those involved in meiosis, testes, and brain function.
  • SRSF12's function is linked to its distinct structural domains and primate-specific expression.