دورية أكاديمية
ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion.
العنوان: | ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion. |
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المؤلفون: | Saulnier O; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France.; Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France., Guedri-Idjouadiene K; University of Liège, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), Liège, Belgium.; University of Liège, GIGA-Molecular Biology of Diseases, Liège, Belgium., Aynaud MM; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Chakraborty A; Institut Curie, PSL Research University, CNRS UMR3348, INSERM U1278, F-91405 Orsay, France.; Université Paris-Saclay, CNRS UMR3348, INSERM U1278, F-91405 Orsay, France.; Équipe Labellisée Ligue Nationale Contre le Cancer, F-91405 Orsay, France., Bruyr J; University of Liège, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), Liège, Belgium.; University of Liège, GIGA-Molecular Biology of Diseases, Liège, Belgium., Pineau J; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., O'Grady T; University of Liège, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), Liège, Belgium.; University of Liège, GIGA-Molecular Biology of Diseases, Liège, Belgium., Mirabeau O; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Grossetête S; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Galvan B; University of Liège, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), Liège, Belgium.; University of Liège, GIGA-Molecular Biology of Diseases, Liège, Belgium., Claes M; University of Liège, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), Liège, Belgium.; University of Liège, GIGA-Molecular Biology of Diseases, Liège, Belgium., Al Oula Hassoun Z; University of Liège, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), Liège, Belgium.; University of Liège, GIGA-Molecular Biology of Diseases, Liège, Belgium., Sadacca B; INSERM U932, RT2Lab Team, Translational Research Department, PSL Research University, Institut Curie, F-75005 Paris, France.; CNRS UMR5219, Institut de Mathématiques de Toulouse; Université de Toulouse; F-31062 Toulouse, France., Laud K; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Zaïdi S; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Surdez D; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Baulande S; Institut Curie, PSL Research University, NGS Platform, 26 rue d'Ulm, F-75005 Paris, France., Rambout X; University of Liège, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), Liège, Belgium.; University of Liège, GIGA-Molecular Biology of Diseases, Liège, Belgium., Tirode F; Claude Bernard University Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon (CRCL), Lyon University, Lyon, France., Dutertre M; Institut Curie, PSL Research University, CNRS UMR3348, INSERM U1278, F-91405 Orsay, France.; Université Paris-Saclay, CNRS UMR3348, INSERM U1278, F-91405 Orsay, France.; Équipe Labellisée Ligue Nationale Contre le Cancer, F-91405 Orsay, France., Delattre O; INSERM U830, Équipe Labellisée LNCC, PSL Research University, SIREDO Oncology Centre, Institut Curie, 75005 Paris, France., Dequiedt F; University of Liège, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), Liège, Belgium.; University of Liège, GIGA-Molecular Biology of Diseases, Liège, Belgium. |
المصدر: | Nucleic acids research [Nucleic Acids Res] 2021 May 21; Vol. 49 (9), pp. 5038-5056. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1992- : Oxford : Oxford University Press Original Publication: London, Information Retrieval ltd. |
مواضيع طبية MeSH: | Alternative Splicing*, Oncogene Proteins, Fusion/*metabolism , Proto-Oncogene Protein c-fli-1/*metabolism , RNA Splicing Factors/*metabolism , RNA-Binding Protein EWS/*metabolism , Repressor Proteins/*metabolism, Calmodulin-Binding Proteins/genetics ; Calmodulin-Binding Proteins/metabolism ; Cell Line ; Cell Line, Tumor ; HeLa Cells ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Protein Domains ; Sarcoma, Ewing/genetics ; Sarcoma, Ewing/metabolism ; Transcriptional Regulator ERG/chemistry ; Transcriptional Regulator ERG/metabolism |
مستخلص: | 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. (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.) |
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المشرفين على المادة: | 0 (ADD3 protein, human) 0 (Calmodulin-Binding Proteins) 0 (ERG protein, human) 0 (EWS-FLI fusion protein) 0 (FLI1 protein, human) 0 (Oncogene Proteins, Fusion) 0 (Proto-Oncogene Protein c-fli-1) 0 (RBFOX2 protein, human) 0 (RNA Splicing Factors) 0 (RNA-Binding Protein EWS) 0 (Repressor Proteins) 0 (Transcriptional Regulator ERG) |
تواريخ الأحداث: | Date Created: 20210519 Date Completed: 20210706 Latest Revision: 20210706 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8136815 |
DOI: | 10.1093/nar/gkab305 |
PMID: | 34009296 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1362-4962 |
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DOI: | 10.1093/nar/gkab305 |