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Publication : EWS splicing regulation contributes to balancing Foxp1 isoforms required for neuronal differentiation.

First Author  Verdile V Year  2022
Journal  Nucleic Acids Res Volume  50
Issue  6 Pages  3362-3378
PubMed ID  35253879 Mgi Jnum  J:323057
Mgi Id  MGI:7260900 Doi  10.1093/nar/gkac154
Citation  Verdile V, et al. (2022) EWS splicing regulation contributes to balancing Foxp1 isoforms required for neuronal differentiation. Nucleic Acids Res 50(6):3362-3378
abstractText  Alternative splicing is a key regulatory process underlying the amplification of genomic information and the expansion of proteomic diversity, particularly in brain. Here, we identify the Ewing sarcoma protein (EWS) as a new player of alternative splicing regulation during neuronal differentiation. Knockdown of EWS in neuronal progenitor cells leads to premature differentiation. Transcriptome profiling of EWS-depleted cells revealed global changes in splicing regulation. Bioinformatic analyses and biochemical experiments demonstrated that EWS regulates alternative exons in a position-dependent fashion. Notably, several EWS-regulated splicing events are physiologically modulated during neuronal differentiation and EWS depletion in neuronal precursors anticipates the splicing-pattern of mature neurons. Among other targets, we found that EWS controls the alternative splicing of the forkhead family transcription factor FOXP1, a pivotal transcriptional regulator of neuronal differentiation, possibly contributing to the switch of gene expression underlying the neuronal differentiation program.
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