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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
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G-quadruplex/m6A-regulated BCL2 pre-mRNA alternative splicing and comparative characterization of its two isoforms
Cuicui Yang1, Shuming Wu1, Hai Wang1
1College of Life Science, Northeast Forestry University, Harbin, 150040, China.
International Journal of Biological Macromolecules
|December 14, 2025
Summary
This study reveals how RNA G-quadruplexes and m6A modification regulate BCL2 splicing, uncovering a new tumor-suppressing role for the BCL2β isoform in breast cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- Alternative splicing of BCL2 pre-mRNA produces BCL2α and BCL2β isoforms.
- BCL2α promotes cancer cell survival, but the splicing mechanism and BCL2β function are unknown.
Purpose of the Study:
- Investigate the mechanisms regulating BCL2 pre-mRNA alternative splicing.
- Determine the functional role of the BCL2β isoform in oncogenesis.
Main Methods:
- Identified RNA G-quadruplex (rG4) and m6A methylation motifs on BCL2 pre-mRNA.
- Utilized in vitro and in cellulo assays to study rG4 structure formation and methylation.
- Investigated the role of SRSF1 as an rG4 binding protein.
Main Results:
- rG4 structure differentially affects BCL2 splicing via m6A modification in TNBC and non-TNBC cells.
- SRSF1 binding to rG4 promotes BCL2α splicing and reduces BCL2β.
- BCL2β exhibits anti-cancer properties, reducing cell survival and migration, and enhancing apoptosis.
Conclusions:
- Uncovered a novel regulatory mechanism of BCL2 alternative splicing involving rG4, m6A, and SRSF1.
- Identified BCL2β as a tumor suppressor with potential therapeutic implications in breast cancer.
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