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Characterization of a new brainâspecific isoform of the EWS oncoprotein
- Melot, Thomas, Dauphinot, Luce, SÃ©venet, Nicolas, Radvanyi, FranÃ§ois, Delattre, Olivier
- European journal of biochemistry 2001 v.268 no.12 pp. 3483-3489
- RNA, adults, alternative splicing, brain, exons, genes, humans, mice, neoplasms, neurons, oncogene proteins, phylogeny, protein synthesis, reverse transcriptase polymerase chain reaction, tissues, transcription factors
- EWS and related TAFII68 and TLS/FUS genes are fused with different genes encoding transcription factors in various human cancers. The products of these genes have the ability to bind RNA and have been shown to be part of splicing and transcription complexes. We show that the EWS, TAFII68 and TLS/FUS proteins are expressed to various levels in all adult murine tissues. We characterize a new isoform of EWS that is specifically expressed in the central nervous system, in both mice and humans. It is shown to be related to a splice variant which includes a new 18âbp exon, termed 4â², between exon 4 and 5. The detection of this isoform in spontaneously differentiating SHâSY5Y neuroblastoma cells and in nerve growth factorâinduced PC12 cells further links this isoform to neural differentiation. RTâPCR experiments indicate that the level of expression ofÂ the brainâspecific EWS isoform is stable during brain development whereas that of the ubiquitous EWS isoform decreases during this period. The two isoforms show a parallel decrease in expression after birth. The 4â² exon is not detected in tumourâspecific EWS fusion transcripts, suggesting that its presence may impair their oncogenic properties. Interestingly, sequences of the 4â² exon and flanking regions show remarkable similarities to that of theÂ neuralâspecific câsrc exon, suggesting common mechanisms for the alternative splicing of these exons. The phylogenetic conservation and relationship to neural differentiation strongly suggests an important functional role for this exon.