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Up-regulation of the proapoptotic caspase 2 splicing isoform by a candidate tumor suppressor, RBM5

Kazuo Fushimi1, Payal Ray, Amar Kar

  • 1Department of Neurology, Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, 303 East Superior Street, Chicago, IL 60611, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 9, 2008
PubMed

Insights

The protein RBM5 binds to caspase 2 (casp-2) pre-mRNA, promoting the proapoptotic Casp-2L isoform. This splicing regulation by RBM5 may contribute to its tumor suppressor activity and offers potential cancer therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • RNA Splicing

Background:

  • Alternative splicing of caspase 2 (casp-2) generates proapoptotic and antiapoptotic isoforms.
  • Programmed cell death (PCD) regulation is crucial in cancer development.

Purpose of the Study:

  • To identify proteins that regulate casp-2 alternative splicing.
  • To investigate the role of RBM5 in casp-2 splicing and its potential tumor suppressor function.

Main Methods:

  • Yeast RNA-protein interaction assay to identify RBM5 binding to casp-2 pre-mRNA.
  • Transfected cell and in vitro splicing assays to assess RBM5's effect on splicing.
  • Mutagenesis experiments to map RBM5 binding sites and functional consequences.

Main Results:

  • RBM5 was identified as a protein that binds to casp-2 pre-mRNA.
  • RBM5 enhances the production of the proapoptotic Casp-2L isoform.
  • RBM5 binds to a specific intronic sequence, regulating the ratio of casp-2 splicing isoforms.

Conclusions:

  • RBM5 is a novel regulator of casp-2 alternative splicing.
  • RBM5-mediated splicing control of casp-2 may contribute to tumor suppression.
  • Targeting splicing regulators like RBM5 could offer new cancer therapies.

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