ArticleMolecular and cellular biology2008
Caffeine regulates alternative splicing in a subset of cancer-associated genes: a role for SC35.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- HIV-1 Tat commandeers nuclear export of Rev-viral RNA complex by controlling hnRNPA2-mediated splicing.Journal of virology · 2023Article
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- Phosphorylation regulates arginine-rich RNA-binding protein solubility and oligomerization.The Journal of biological chemistry · 2021Article
- Article
- Splicing factor SRSF2-centric gene regulation.International journal of biological sciences · 2021Review
- Serine/arginine-rich splicing factors: the bridge linking alternative splicing and cancer.International journal of biological sciences · 2020Review
- Caffeine boosts Ataluren's readthrough activity.Heliyon · 2019Article
- Regulatory mechanisms of incomplete huntingtin mRNA splicing.Nature communications · 2018Article
- Therapeutic Applications of Targeted Alternative Splicing to Cancer Treatment.International journal of molecular sciences · 2017Review
- Theophylline exhibits anti-cancer activityOncotarget · 2017Article
- Optogenetic protein clustering through fluorescent protein tagging and extension of CRY2.Nature communications · 2017Article
- A Cytoplasmic RNA Virus Alters the Function of the Cell Splicing Protein SRSF2.Journal of virology · 2017Article
- Pharmacology of Modulators of Alternative Splicing.Pharmacological reviews · 2017Review
- SF3A1 and pancreatic cancer: new evidence for the association of the spliceosome and cancer.Oncotarget · 2015Article
- Methylxanthines Increase Expression of the Splicing Factor SRSF2 by Regulating Multiple Post-transcriptional Mechanisms.The Journal of biological chemistry · 2015Article
- KLF6 loss of function in human prostate cancer progression is implicated in resistance to androgen deprivation.The American journal of pathology · 2012Article
- The application of nonsense-mediated mRNA decay inhibition to the identification of breast cancer susceptibility genes.BMC cancer · 2012Article
- Xanthines down-regulate the drug transporter ABCG2 and reverse multidrug resistance.Molecular pharmacology · 2012Article
- Exon 11 skipping of E-cadherin RNA downregulates its expression in head and neck cancer cells.Molecular cancer therapeutics · 2011Article
- The DNA damage response pathway regulates the alternative splicing of the apoptotic mediator Bcl-x.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Alternative splicing of pre-mRNA contributes significantly to human proteomic complexity, playing a key role in development, gene expression and, when aberrant, human disease onset. Many of the factors involved in alternative splicing have been identified, but little is known about their regulation. Here we report that caffeine regulates alternative splicing of a subset of cancer-associated genes, including the tumor suppressor KLF6. This regulation is at the level of splice site selection, occurs rapidly and reversibly, and is concentration dependent. We have recapitulated caffeine-induced alternative splicing of KLF6 using a cell-based minigene assay and identified a "caffeine response element" within the KLF6 intronic sequence. Significantly, a chimeric minigene splicing assay demonstrated that this caffeine response element is functional in a heterologous context; similar elements exist within close proximity to caffeine-regulated exons of other genes in the subset. Furthermore, the SR splicing factor, SC35, was shown to be required for induction of the alternatively spliced KLF6 transcript. Importantly, SC35 is markedly induced by caffeine, and overexpression of SC35 is sufficient to mimic the effect of caffeine on KLF6 alternative splicing. Taken together, our data implicate SC35 as a key player in caffeine-mediated splicing regulation. This novel effect of caffeine provides a valuable tool for dissecting the regulation of alternative splicing of a large gene subset and may have implications with respect to splice variants associated with disease states.
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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.