ArticleNucleic acids research2014
Regulation of BCL-X splicing reveals a role for the polypyrimidine tract binding protein (PTBP1/hnRNP I) in alternative 5' splice site selection.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021Pooled it
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- Anti-apoptotic BCL-2 family proteins: from regulatory networks to therapeutic targeting.Oncogenesis · 2026Review
- Exon inclusion signatures enable accurate estimation of splicing factor activity.Nature communications · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- SRSF9 mediates oncogenic RNA splicing of SLC37A4 via liquid-liquid phase separation to promote oral cancer progression.Journal of advanced research · 2026Article
- Identification and functional characterization of splicing factors implicated in mantle cell lymphoma aggressiveness.Scientific reports · 2025Article
- Exon inclusion signatures enable accurate estimation of splicing factor activity.bioRxiv : the preprint server for biology · 2025Article
- PTBP1 and Cancer: From RNA Regulation to Therapeutic Potential.Journal of cellular and molecular medicine · 2025Review
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- Splicing to orchestrate cell fate.Molecular therapy. Nucleic acids · 2025Review
- Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer.Cancers · 2025Review
- Biological relevance of alternative splicing in hematologic malignancies.Molecular medicine (Cambridge, Mass.) · 2024Review
- Alternative splicing of BCL-x is controlled by RBM25 binding to a G-quadruplex in BCL-x pre-mRNA.Nucleic acids research · 2023Article
- Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method.Scientific reports · 2023Article
- Reviewing PTBP1 Domain Modularity in the Pre-Genomic Era: A Foundation to Guide the Next Generation of Exploring PTBP1 Structure-Function Relationships.International journal of molecular sciences · 2023Review
- LncRNA BCLET variant confers bladder cancer susceptibility through alternative splicing of MSANTD2 exon 1.Cancer medicine · 2023Article
- RNA splicing dysregulation and the hallmarks of cancer.Nature reviews. Cancer · 2023Review
- hsa_circ_0005358 suppresses cervical cancer metastasis by interacting with PTBP1 protein to destabilize CDCP1 mRNA.Molecular therapy. Nucleic acids · 2022Article
- SF3B1 inhibition disrupts malignancy and prolongs survival in glioblastoma patients through BCL2L1 splicing and mTOR/ß-catenin pathways imbalances.Journal of experimental & clinical cancer research : CR · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative splicing (AS) modulates many physiological and pathological processes. For instance, AS of the BCL-X gene balances cell survival and apoptosis in development and cancer. Herein, we identified the polypyrimidine tract binding protein (PTBP1) as a direct regulator of BCL-X AS. Overexpression of PTBP1 promotes selection of the distal 5' splice site in BCL-X exon 2, generating the pro-apoptotic BCL-Xs splice variant. Conversely, depletion of PTBP1 enhanced splicing of the anti-apoptotic BCL-XL variant. In vivo cross-linking experiments and site-directed mutagenesis restricted the PTBP1 binding site to a polypyrimidine tract located between the two alternative 5' splice sites. Binding of PTBP1 to this site was required for its effect on splicing. Notably, a similar function of PTBP1 in the selection of alternative 5' splice sites was confirmed using the USP5 gene as additional model. Mechanistically, PTBP1 displaces SRSF1 binding from the proximal 5' splice site, thus repressing its selection. Our study provides a novel mechanism of alternative 5' splice site selection by PTBP1 and indicates that the presence of a PTBP1 binding site between two alternative 5' splice sites promotes selection of the distal one, while repressing the proximal site by competing for binding of a positive regulator.
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