Article (Scientific journals)
ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion
Saulnier, Olivier; Guedri, Katia; Aynaud, Marie-Ming et al.
2021In Nucleic Acids Research
Peer Reviewed verified by ORBi
 

Files


Full Text
ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion.pdf
Publisher postprint (2.76 MB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
ERG; Alternative splicing; RBFOX2; EWS-FLI1; Ewing sarcoma
Abstract :
[en] ERG family proteins (ERG, FLI1 and FEV) are a sub- family 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 asso- ciate 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) en- riched with RBFOX2 motifs and co-regulated by this splicing factor. ERG and FLI1 are associated with RB- FOX2 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 antag- onizes RBFOX2 effects on exon inclusion. In particu- lar, 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Saulnier, Olivier 
Guedri, Katia  ;  Université de Liège - ULiège > Doct. sc. (bioch., biol. mol.&cell., bioinf.&mod.-Bologne)
Aynaud, Marie-Ming
Chakraborty, Alina
Bruyr, Jonathan ;  Université de Liège - ULiège > GIGA Molecul. Biolog. of Diseases - Gene Expression & Cancer
Pineau, Joséphine
O’Grady, Tina
Mirabeau, Olivier
Grossetête, Sandrine
Galvan, Bartimée  ;  Université de Liège - ULiège > Form. doct. sc. (bioch., biol. mol. cel., bioinf. - paysage)
Claes, Margaux ;  Université de Liège - ULiège > Form. doct. sc. (bioch., biol. mol. cel., bioinf. - paysage)
Hassoun, Zahrat El Oula Ghassan ;  Université de Liège - ULiège > Form. doct. sc. (bioch., biol. mol. cel., bioinf. - paysage)
Sadacca, Benjamin
Laud, Karine
Zaïdi, Sakina
Surdez, Didier
Baulande, Sylvain
Rambout, Xavier
Tirode, Franck
Dutertre, Martin 
Delattre, Olivier 
Dequiedt, Franck   ;  Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
More authors (12 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion
Publication date :
01 May 2021
Journal title :
Nucleic Acids Research
ISSN :
0305-1048
eISSN :
1362-4962
Publisher :
Oxford University Press, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
The authors wish it to be known that, in their opinion, the first two and last three authors should be regarded as Joint First and Joint Last Authors, respectively.
Available on ORBi :
since 17 June 2021

Statistics


Number of views
161 (19 by ULiège)
Number of downloads
151 (15 by ULiège)

Scopus citations®
 
9
Scopus citations®
without self-citations
8
OpenCitations
 
4

Bibliography


Similar publications



Contact ORBi