Skip to content
Open access

RERE and the Mediator complex cooperate with EWSR1::FLI1 in the reprogramming of Translation and Alternative Splicing, the latter being a therapeutically targetable vulnerability in Ewing sarcoma

Aug 2026 · bioRxiv · 0 citations
Biology

TL;DR

The identification of the splicing factor RBM39 as a vulnerability in ES is supported by the extraordinary sensitivity of these tumors to monotherapy with RBM39 degrader indisulam, highlighting the potential of this approach as a novel and promising therapeutic strategy for Ewing sarcoma.

Read PDF

Similar papers

Sep 2026

Abstract B024: The EWSR1 low complexity domain drives cooperative DNA binding of EWSR1::FLI1 to multiple GGAA repeats

Ewing Sarcoma is defined by its hallmark mutation, a t(11;22)q24;q12) translocation which results in fusion of the EWSR1 and FLI1 genes. The fusion product, EWSR1::FLI1, contains the N-terminal low complexity domain (LCD) of EWSR1 and the DNA-binding Domain (DBD) of FLI1. EWSR1::FLI1 binds at microsatellites (µsats),...

Caleb J. Frye, R. Zhou, Lexis R. Rice et al. · 0 citations
Sep 2026

Abstract B025: Multiple domains contribute to nucleosome invasion by EWSR1::FLI1

Ewing sarcoma is a rare and aggressive pediatric cancer caused by a translocation-derived fusion oncoprotein that fuses the N-terminal low complexity domain (LCD) of a FET protein (FUS, EWSR1, or TAF15) with the C-terminal portion of an ETS transcription factor from the ERG or PEA3 subfamilies. These fusion oncoprote...

Ruo-Wen Chen, R. Zhou, E. J. Tokarsky et al. · 0 citations
Open access Sep 2026

Fusion Oncoprotein EWSR1::FLI1 Invades Nucleosomes at Consensus ETS Motifs and GGAA Microsatellites

Ewing sarcoma is an aggressive bone malignancy occurring in children, adolescents, and young adults. Most cases are caused by expression of the fusion oncoprotein EWSR1::FLI1, which contains the low complexity domain (LCD) of EWSR1 and the DNA-binding domain (DBD) of FLI1. Previous genomic studies indicate EWSR1::FLI1...

Ruo-Wen Chen, R. Zhou, E. J. Tokarsky et al. · 0 citations
Open access Aug 2026

SNHG family lncRNAs promote Ewing sarcoma cell fitness through intronic snoRNA-guided rRNA modifications

Abstract Over 90% of Ewing sarcomas (EWS) are driven by the EWS–FLI1 fusion oncoprotein. EWS–FLI1 acts as a pioneer transcription factor, altering the expression of hundreds of genes including many long non-coding RNAs (lncRNAs). The role of these lncRNAs in the oncogenesis of EWS is mostly unknown. We developed a CRIS...

Marcela Briones-Martin-Del-Campo, Alex G. Lee, Truc Dinh et al. · 0 citations
Open access Aug 2026

Targeting of the oncogenic fusion EWSR1-FLI1 in Ewing Sarcoma by CRISPR/dCas9 silencers.

Despite the revolutionary impact of genome engineering tools in medicine, the safe and effective intracellular delivery of CRISPR remains a major obstacle for clinical applications. Here, we utilize precision molecular targeting and delivery strategies based on CRISPR/dCas9 systems adapted for epigenetic repression (dC...

Shahama Taifour, Chee-Wai Wong, Christopher P. Wallis et al. · 0 citations
Open access Sep 2026

The Drosophila FET ortholog Cabeza is an essential cofactor for ETV4-mediated activation of GGAA microsatellite neoenhancers.

The conversion of transcriptionally silent GGAA microsatellites (GGAAµSats) into functional enhancers by FET::ETS oncogenic fusions is a hallmark of Ewing sarcoma. However, emerging evidence implicates non-fused, full-length oncogenic ETS transcription factors in activating these repeats in other malignancies. Evaluati...

Cristina Molnar, Jose Reina, J. Mora et al. · 0 citations

We use cookies to run the site and, with your consent, for analytics and to show ads. See our Cookie Policy.