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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
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An alternative splicing event amplifies evolutionary differences between vertebrates.

Serge Gueroussov1, Thomas Gonatopoulos-Pournatzis2, Manuel Irimia3

  • 1Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

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|August 22, 2015
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Summary
This summary is machine-generated.

Mammalian-specific alternative splicing of PTBP1 exon 9 alters its regulatory activity, driving numerous splicing changes and contributing to vertebrate nervous system evolution.

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Genomics

Background:

  • Alternative splicing (AS) creates extensive transcriptomic and proteomic diversity.
  • The functional roles of species-specific splice variants remain largely unexplored.

Purpose of the Study:

  • To investigate the functional impact of mammalian-specific alternative splicing of polypyrimidine tract-binding protein 1 (PTBP1) exon 9.
  • To understand how this single exon-skipping event influences broader splicing programs and evolutionary divergence.

Main Methods:

  • Analysis of PTBP1 exon 9 skipping in mammalian cells and its effect on downstream splicing.
  • Experimental induction of orthologous exon skipping in chicken cells.
  • Comparative analysis of splicing changes between species.

Main Results:

  • Mammalian-specific skipping of PTBP1 exon 9 modifies PTBP1's splicing regulatory functions.
  • This exon skipping reduces PTBP1's repressive activity, promoting a brain-specific AS program during neurogenesis.
  • Engineered skipping of the corresponding exon in chicken cells recapitulates mammalian-like AS changes in PTBP1 targets.

Conclusions:

  • A single exon-skipping event in an RNA-binding regulator can orchestrate widespread AS changes across species.
  • These AS alterations likely played a role in the evolutionary divergence of vertebrate nervous systems.