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. |