ArticlePloS one2014
Identification of cis-acting elements and splicing factors involved in the regulation of BIM Pre-mRNA splicing.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The effect of BIM deletion polymorphism on intrinsic resistance and clinical outcome of cancer patient with kinase inhibitor therapy.Scientific reports · 2015Pooled it
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- Regulation of Tau Alternative Splicing: A Novel Role for the Ribonucleoprotein RBM20.International journal of molecular sciences · 2026Article
- The therapeutic potential and mechanisms of targeting the PTBP1/Nogo-A/NgR axis in PTSD induced by single prolonged stress in mice.Experimental & molecular medicine · 2026Article
- PTBP1 and Cancer: From RNA Regulation to Therapeutic Potential.Journal of cellular and molecular medicine · 2025Review
- Best evidence linking the extracellular factor TGF-β to cancer-associated alternative splicing programs.BBA advances · 2025Review
- Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.Diabetologia · 2024Article
- Biological relevance of alternative splicing in hematologic malignancies.Molecular medicine (Cambridge, Mass.) · 2024Review
- Polypyrimidine Tract Binding Protein: A Universal Player in Cancer Development.Current molecular medicine · 2024Review
- The effects of mutations on gene expression and alternative splicing.Proceedings. Biological sciences · 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
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Genetic variant rs10251977 (G>A) in EGFR-AS1 modulates the expression of EGFR isoforms A and D.Scientific reports · 2021Article
- PTBP1 contributes to spermatogenesis through regulation of proliferation in spermatogonia.The Journal of reproduction and development · 2019Article
- Alternative-splicing defects in cancer: Splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics.Wiley interdisciplinary reviews. RNA · 2018Review
- Overcoming imatinib resistance conferred by theOncotarget · 2017Article
- Differential Impacts of Alternative Splicing Networks on Apoptosis.International journal of molecular sciences · 2016Review
- The Role of Alternative Splicing in the Control of Immune Homeostasis and Cellular Differentiation.International journal of molecular sciences · 2015Review
- Regulation of Bim in Health and Disease.Oncotarget · 2015Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant changes in the expression of the pro-apoptotic protein, BCL-2-like 11 (BIM), can result in either impaired or excessive apoptosis, which can contribute to tumorigenesis and degenerative disorders, respectively. Altering BIM pre-mRNA splicing is an attractive approach to modulate apoptosis because BIM activity is partly determined by the alternative splicing of exons 3 or 4, whereby exon 3-containing transcripts are not apoptotic. Here we identified several cis-acting elements and splicing factors involved in BIM alternative splicing, as a step to better understand the regulation of BIM expression. We analyzed a recently discovered 2,903-bp deletion polymorphism within BIM intron 2 that biased splicing towards exon 3, and which also impaired BIM-dependent apoptosis. We found that this region harbors multiple redundant cis-acting elements that repress exon 3 inclusion. Furthermore, we have isolated a 23-nt intronic splicing silencer at the 3' end of the deletion that is important for excluding exon 3. We also show that PTBP1 and hnRNP C repress exon 3 inclusion, and that downregulation of PTBP1 inhibited BIM-mediated apoptosis. Collectively, these findings start building our understanding of the cis-acting elements and splicing factors that regulate BIM alternative splicing, and also suggest potential approaches to alter BIM splicing for therapeutic purposes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.