Fusion protein EWS-FLI1 is incorporated into a protein granule in cells
AuthorAhmed, Nasiha S.
Harrell, Lucas M.
Wieland, Daniel R.
Lay, Michelle A.
Thompson, Valery F.
Schwartz, Jacob C.
AffiliationDepartment of Molecular and Cellular Biology, University of Arizona
Department of Chemistry and Biochemistry, University of Arizona
MetadataShow full item record
PublisherCold Spring Harbor Laboratory
CitationAhmed, N. S., Harrell, L. M., Wieland, D. R., Lay, M. A., Thompson, V. F., & Schwartz, J. C. (2021). Fusion protein EWS-FLI1 is incorporated into a protein granule in cells. RNA, 27(8), 920–932.
RightsCopyright © 2021 Ahmed et al. This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
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AbstractEwing sarcoma is driven by fusion proteins containing a low-complexity (LC) domain that is intrinsically disordered and a powerful transcriptional regulator. The most common fusion protein found in Ewing sarcoma, EWS-FLI1, takes its LC domain from the RNA-binding protein EWSR1 (Ewing sarcoma RNA-binding protein 1) and a DNA-binding domain from the transcription factor FLI1 (Friend leukemia virus integration 1). EWS-FLI1 can bind RNA polymerase II (RNA Pol II) and self-assemble through its LC domain. The ability of RNA-binding proteins like EWSR1 to self-assemble or phase separate in cells has raised questions about the contribution of this process to EWS-FLI1 activity. We examined EWSR1 and EWS-FLI1 activity in Ewing sarcoma cells by siRNA-mediated knockdown and RNA-seq analysis. More transcripts were affected by the EWSR1 knockdown than expected and these included many EWS-FLI1 regulated genes. We reevaluated physical interactions between EWS-FLI1, EWSR1, and RNA Pol II, and used a cross-linking-based strategy to investigate protein assemblies associated with the proteins. The LC domain of EWS-FLI1 was required for the assemblies observed to form in cells. These results offer new insights into a protein assembly that may enable EWS-FLI1 to bind its wide network of protein partners and contribute to regulation of gene expression in Ewing sarcoma.
NoteOpen access article
VersionFinal published version
SponsorsNational Institutes of Health
Except where otherwise noted, this item's license is described as Copyright © 2021 Ahmed et al. This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
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