Fusion protein EWS-FLI1 is incorporated into a protein granule in cells
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RNA-2021-Ahmed-920-32.pdf
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Author
Ahmed, Nasiha S.Harrell, Lucas M.
Wieland, Daniel R.
Lay, Michelle A.
Thompson, Valery F.
Schwartz, Jacob C.
Affiliation
Department of Molecular and Cellular Biology, University of ArizonaDepartment of Chemistry and Biochemistry, University of Arizona
Issue Date
2021-05-25
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Cold Spring Harbor LaboratoryCitation
Ahmed, 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.Journal
RNARights
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/.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Ewing 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.Note
Open access articleISSN
1355-8382EISSN
1469-9001PubMed ID
34035145Version
Final published versionSponsors
National Institutes of Healthae974a485f413a2113503eed53cd6c53
10.1261/rna.078827.121
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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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