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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

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Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation

Elena Martín1,2, Claudia Vivori1,2, Malgorzata Rogalska1

  • 1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona 08003, Spain.

RNA (New York, N.Y.)
|September 21, 2021
PubMed

Insights

Three splicing factors, SPF45, SR140, and CHERP, form a complex regulating alternative splicing. This impacts cell division and cancer proliferation by controlling key cell-cycle genes like FOXM1.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Pre-mRNA processing is crucial for cell division and cancer proliferation, yet its molecular regulation is not fully understood.
  • Alternative splicing plays a significant role in gene expression and cellular functions.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying pre-mRNA processing in cell division and cancer proliferation.
  • To identify key splicing factors and their roles in regulating alternative splicing events.

Main Methods:

  • Co-immunoprecipitation to identify protein complexes.
  • RNA sequencing to analyze alternative splicing events.
  • siRNA-mediated knockdown to assess functional consequences.

Main Results:

  • SPF45, SR140, and CHERP form a stable complex that regulates alternative splicing.
  • This complex frequently represses short exons with suboptimal 3' splice sites.
  • Knockdown of these factors causes G2/M cell-cycle arrest and apoptosis in HeLa cells.
  • Altered splicing of FOXM1 and SPDL1 partially explains the observed effects on cell proliferation.

Conclusions:

  • The SPF45/SR140/CHERP complex is a critical regulator of alternative splicing essential for cell proliferation.
  • Dysregulation of this complex impacts cell-cycle progression and may contribute to cancer development.
  • Targeting this splicing complex could offer new therapeutic strategies for cancer treatment.
Keywords:
CHERPSPF45SR140alternative splicingcell proliferation

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