ArticleNucleic acids research2021
ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Exploring Resistance to ETS Targeting Agents in Diffuse Large B-Cell Lymphoma.Cancer medicine · 2026Article
- A Novel FLI1 Monoclonal Antibody Which Recognizes EWS::FLI1 with High Affinity Is Useful for Detecting Ewing Sarcoma.Antibodies (Basel, Switzerland) · 2025Article
- Subversion of mRNA degradation pathways by EWSR1::FLI1 represents a therapeutic vulnerability in Ewing sarcoma.Nature communications · 2025Article
- Synergistic DNA and RNA binding of the Hox transcription factor Ultrabithorax coordinates splicing and shapes in vivo homeotic functions.Nucleic acids research · 2025Article
- ERG transcriptionally activates SFRP1 to promote apoptosis of keloid fibroblasts and inhibit epithelial-mesenchymal transition and fibrosis through the Wnt3a/β-catenin pathway.Archives of dermatological research · 2025Article
- YK-4-279 Induces Osteosarcoma Cell Cycle Arrest, DNA Damage Response, and Apoptosis by Regulating the MAPK Cascade.Drug design, development and therapy · 2025Article
- Lamin B1 regulates RNA splicing factor expression by modulating the spatial positioning and chromatin interactions of theAnimal cells and systems · 2025Article
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
- Expanding the clinicopathologic spectrum and genomic landscape of tumors with SMARCA2/4::CREM fusions.The Journal of pathology · 2024Article
- RNA splicing factor RBFOX2 is a key factor in the progression of cancer and cardiomyopathy.Clinical and translational medicine · 2024Review
- A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing.Nature cell biology · 2024Article
- Cell-type specific regulator RBPMS switches alternative splicing via higher-order oligomerization and heterotypic interactions with other splicing regulators.Nucleic acids research · 2023Article
- MS0621, a novel small-molecule modulator of Ewing sarcoma chromatin accessibility, interacts with an RNA-associated macromolecular complex and influences RNA splicing.Frontiers in oncology · 2023Article
- The transcription factor c-Jun inhibits RBM39 to reprogram pre-mRNA splicing during genotoxic stress.Nucleic acids research · 2022Article
- FOXA1 regulates alternative splicing in prostate cancer.Cell reports · 2022Article
- Comprehensive profiling of mRNA splicing indicates that GC content signals altered cassette exon inclusion in Ewing sarcoma.NAR cancer · 2022Article
- HOX Protein Activity Regulation by Cellular Localization.Journal of developmental biology · 2021Review
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ERG family proteins (ERG, FLI1 and FEV) are a subfamily of ETS transcription factors with key roles in physiology and development. In Ewing sarcoma, the oncogenic fusion protein EWS-FLI1 regulates both transcription and alternative splicing of pre-messenger RNAs. However, whether wild-type ERG family proteins might regulate splicing is unknown. Here, we show that wild-type ERG proteins associate with spliceosomal components, are found on nascent RNAs, and induce alternative splicing when recruited onto a reporter minigene. Transcriptomic analysis revealed that ERG and FLI1 regulate large numbers of alternative spliced exons (ASEs) enriched with RBFOX2 motifs and co-regulated by this splicing factor. ERG and FLI1 are associated with RBFOX2 via their conserved carboxy-terminal domain, which is present in EWS-FLI1. Accordingly, EWS-FLI1 is also associated with RBFOX2 and regulates ASEs enriched in RBFOX2 motifs. However, in contrast to wild-type ERG and FLI1, EWS-FLI1 often antagonizes RBFOX2 effects on exon inclusion. In particular, EWS-FLI1 reduces RBFOX2 binding to the ADD3 pre-mRNA, thus increasing its long isoform, which represses the mesenchymal phenotype of Ewing sarcoma cells. Our findings reveal a RBFOX2-mediated splicing regulatory function of wild-type ERG family proteins, that is altered in EWS-FLI1 and contributes to the Ewing sarcoma cell phenotype.
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