ArticleProceedings of the National Academy of Sciences of the United States of America2002
Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 126 citations in OpenAlex.
- Genetic alternative splicing regulation mapping of cartilage and synovium reveals tissue-specific mechanisms of joint-related traits.Nature communications · 2026Article
- Alternative Splicing in Embryo Implantation.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2025Review
- Alternative splicing is coupled to gene expression in a subset of variably expressed genes.NPJ genomic medicine · 2024Article
- Alternative splicing is coupled to gene expression in a subset of variably expressed genes.bioRxiv : the preprint server for biology · 2023Article
- Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors.Life (Basel, Switzerland) · 2023Review
- Genome-wide identification of associations between enhancer and alternative splicing in human and mouse.BMC genomics · 2022Article
- Tau mRNA Metabolism in Neurodegenerative Diseases: A Tangle Journey.Biomedicines · 2022Review
- VEGFA's distal enhancer regulates its alternative splicing in CML.NAR cancer · 2021Article
- A machine learning-based framework for modeling transcription elongation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Reciprocal regulation between alternative splicing and the DNA damage response.Genetics and molecular biology · 2020Article
- A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.Journal of experimental & clinical cancer research : CR · 2019Article
- RBM47-regulated alternative splicing of TJP1 promotes actin stress fiber assembly during epithelial-to-mesenchymal transition.Oncogene · 2019Article
- Past, present, and future of circRNAs.The EMBO journal · 2019Review
- Alternative splicing of neuronal genes: new mechanisms and new therapies.Current opinion in neurobiology · 2019Review
- The importance of DNA methylation of exons on alternative splicing.RNA (New York, N.Y.) · 2018Article
- Beyond Transcription: Roles of Transcription Factors in Pre-mRNA Splicing.Chemical reviews · 2018Review
- Alternative promoter usage generates novel shorter MAPT mRNA transcripts in Alzheimer's disease and progressive supranuclear palsy brains.Scientific reports · 2017Article
- LOX-1 and Its Splice Variants: A New Challenge for Atherosclerosis and Cancer-Targeted Therapies.International journal of molecular sciences · 2017Review
- Increased global transcription activity as a mechanism of replication stress in cancer.Nature communications · 2016Article
- A semi-supervised approach uncovers thousands of intragenic enhancers differentially activated in human cells.BMC genomics · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Promoters and enhancers are cis-acting elements that control gene transcription via complex networks of protein-DNA and protein-protein interactions. Whereas promoters deal with putting in place the RNA polymerase, both enhancers and promoters can control transcriptional initiation and elongation. We have previously shown that promoter structure modulates alternative splicing, strengthening the concept of a physical and functional coupling between transcription and splicing. Here we report that the promoter effect is due to the control of RNA pol II elongation. We found that the simian virus 40 (SV40) transcriptional enhancer, inserted in fibronectin (FN) minigene constructs transfected into mammalian cells, controls alternative splicing by inhibiting inclusion of the FN extra domain I (EDI) exon into mature mRNA. Deletion analysis of enhancer subdomains and competitions in vivo with excess of specific enhancer DNA subfragments demonstrate that the "minimal" enhancer, consisting of two 72-bp repeats, is responsible for the splicing effect. The 72-bp repeat region has been reported to promote RNA pol II elongation. When transcription is driven by the alpha-globin promoter linked to the SV40 enhancer, basal EDI inclusion and activation by the SR (Ser-Arg-rich) protein SF2/ASF are much lower than with other promoters. Deletion of only one of the two 72-bp repeats not only provokes higher EDI inclusion levels but allows responsiveness to SF2/ASF. These effects are the consequence of a decrease in RNA pol II elongation evidenced both by an increase in the proportions of shorter proximal over full length transcripts and by higher pol II densities upstream of the alternative exon detected by chromatin immunoprecipitation.
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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.