ArticleJournal of molecular cell biology2012
Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons.
Article in Journal of molecular cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 122 citations in OpenAlex.
- SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting the KIFC1-SRSF3-PKM Axis Suppresses Cervical Cancer Glycolysis and Enhances Radiosensitivity.Journal of cellular and molecular medicine · 2026Article
- Review
- ASO-based PKM splice-switching therapy increases anti-CTLA-4 antibody efficacy in pancreatic ductal adenocarcinoma.Cell discovery · 2026Article
- RNA-coupled CRISPR screens reveal ZNF207 as a regulator of LMNA aberrant splicing in progeria.Molecular cell · 2026Article
- Isoforms in action: The impact of transcript diversity in phenotype.Genetics and molecular biology · 2026Article
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Article
- The denitrosylase SCoR2 controls cardioprotective metabolic reprogramming.bioRxiv : the preprint server for biology · 2025Article
- Alternative Splicing of BnABF4L Mediates Response to Abiotic Stresses in Rapeseed (Brassica napus L.).Biotechnology for biofuels and bioproducts · 2025Article
- Review
- Antisense oligonucleotide-mediated TRA2β poison exon inclusion induces the expression of a lncRNA with anti-tumor effects.Nature communications · 2025Article
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- A CRISPR-dCas13 RNA-editing tool to study alternative splicing.Nucleic acids research · 2024Article
- Screening Splice-Switching Antisense Oligonucleotides in Pancreas-Cancer Organoids.Nucleic acid therapeutics · 2024Article
- The Regulatory Network of hnRNPs Underlying RegulatingBiomolecules · 2024Review
- CD8+ T cell metabolic flexibility elicited by CD28-ARS2 axis-driven alternative splicing of PKM supports antitumor immunity.Cellular & molecular immunology · 2024Article
- Intronic miR-6741-3p targets the oncogene SRSF3: Implications for oral squamous cell carcinoma pathogenesis.PloS one · 2024Article
- Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications.Current medicinal chemistry · 2024Review
- RNA splicing dysregulation and the hallmarks of cancer.Nature reviews. Cancer · 2023Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Alternative splicing of the pyruvate kinase M gene (PK-M) can generate the M2 isoform and promote aerobic glycolysis and tumor growth. However, the cancer-specific alternative splicing regulation of PK-M is not completely understood. Here, we demonstrate that PK-M is regulated by reciprocal effects on the mutually exclusive exons 9 and 10, such that exon 9 is repressed and exon 10 is activated in cancer cells. Strikingly, exonic, rather than intronic, cis-elements are key determinants of PK-M splicing isoform ratios. Using a systematic sub-exonic duplication approach, we identify a potent exonic splicing enhancer in exon 10, which differs from its homologous counterpart in exon 9 by only two nucleotides. We identify SRSF3 as one of the cognate factors, and show that this serine/arginine-rich protein activates exon 10 and mediates changes in glucose metabolism. These findings provide mechanistic insights into the complex regulation of alternative splicing of a key regulator of the Warburg effect, and also have implications for other genes with a similar pattern of alternative splicing.
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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.