2026-04-17T06:11:39Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/237222025-12-12T01:40:57Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Paronetto, Maria Paola author Bernardis, Isabella author Volpe, Elisabetta author Bechara, Elias author Sebestyén, Endre author Eyras Jiménez, Eduardo author Valcárcel, J. (Juan) author 2015-06-04T06:56:36Z 2015-06-04T06:56:36Z 2014 The Ewing sarcoma protein EWS is an RNA and DNA binding protein implicated in transcription, pre-mRNA splicing, and DNA damage response. Using CLIP-seq, we identified EWS RNA binding sites in exonic regions near 5′ splice sites. A prominent target was exon 6 of the FAS/CD95 receptor, which is alternatively spliced to generate isoforms with opposing activities in programmed cell death. Depletion and overexpression experiments showed that EWS promotes exon 6 inclusion and consequently the synthesis of the proapoptotic FAS/CD95 isoform, whereas an EWS-FLI1 fusion protein characteristic of Ewing sarcomas shows decreased activity. Biochemical analyses revealed that EWS binding promotes the recruitment of U1snRNP and U2AF65 to the splice sites flanking exon 6 and therefore exon definition. Consistent with a role for EWS in the regulation of programmed cell death, cells depleted of EWS show decreased sensitivity to FAS-induced apoptosis, and elevated EWS expression enhances apoptosis in EWS-haploinsufficient Ewing sarcoma cells. M.P.P. was supported by a fellowship from the HFSP. This project was supported by Fundación Botín, Fundación Sandra Ibarra (FSI2013), the European Union Sixth Framework Programme under grant agreement Nr. LSHG-CT-2005-518238-V (EURASNET), the Spanish Ministry of Economy and Competitiveness (grant no. CSD2009-00080, Consolider RNAREG/BFU2011-29583 / BIO2011-23920), and AIRC (Grant MFAG 11658). We also acknowledge support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013-2017” (SEV-2012-0208) Proteïnes Antígens CD RNA Regulation of FAS exon definition and apoptosis by the ewing sarcoma protein