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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Translocation of a Cell Surface Spliceosomal Complex Induces Alternative Splicing Events and Lymphoma Cell Necrosis

Sonal S Tonapi1, Vaishali Pannu1, Janet E Duncan1

  • 1Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.

Cell Chemical Biology
|April 2, 2019
PubMed

Insights

Researchers discovered a surface spliceosomal complex (SSC) on lymphoma cells. Targeting this complex with aptamers induces cell death, revealing a novel cancer therapy target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Spliceosomal dysregulation is implicated in cancer, driving interest in targeting intracellular spliceosomal proteins.
  • Alternative splicing impacts critical cellular processes like signal transduction, metabolism, and proliferation.

Purpose of the Study:

  • To investigate the novel finding of a spliceosomal complex located on the surface of lymphoma cells.
  • To characterize the surface spliceosomal complex (SSC) and its role in cancer cell survival and death.

Main Methods:

  • Discovery of the SSC through its identification as the binding target of the C10.36 aptamer.
  • Analysis of SSC composition, involving at least 13 core spliceosomal components.
  • Investigating the functional consequences of aptamer-mediated SSC internalization.

Main Results:

  • A subset of lymphoma cells exhibits a surface spliceosomal complex (SSC).
  • The aptamer C10.36 binds to SSC, triggering its internalization into the cell.
  • Internalization of SSC leads to widespread alterations in alternative splicing patterns.
  • These splicing changes ultimately result in necrotic cell death.

Conclusions:

  • The study reveals an unprecedented spatial organization of a spliceosomal complex on the cell surface.
  • The SSC represents a promising novel target for anti-cancer drug development, particularly for lymphoma.
  • The localization of the SSC is crucial for cancer cell survival, offering new therapeutic strategies.
Keywords:
AP-MSG-quadruplexaffinity labelingalternative splicingaptamercancernon-Hodgkin’s lymphomaribonucleoproteinsspliceosome

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