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.

Verdile, V., Svetoni, F., La Rosa, P., Ferrante, G., Cesari, E., Sette, C., Paola Paronetto, M., EWS splicing regulation contributes to balancing Foxp1 isoforms required for neuronal differentiation, <<NUCLEIC ACIDS RESEARCH>>, 2022; 2022 (gkac154): 154-170. [doi:10.1093/nar/gkac154] [http://hdl.handle.net/10807/198025]

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

Cesari, Eleonora;Sette, Claudio
Penultimo
;
2022

Abstract

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.
Inglese
Verdile, V., Svetoni, F., La Rosa, P., Ferrante, G., Cesari, E., Sette, C., Paola Paronetto, M., EWS splicing regulation contributes to balancing Foxp1 isoforms required for neuronal differentiation, <<NUCLEIC ACIDS RESEARCH>>, 2022; 2022 (gkac154): 154-170. [doi:10.1093/nar/gkac154] [http://hdl.handle.net/10807/198025]
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