FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells

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2020-03-13Author
Smith, Jean A.
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Curry, Ennessa G.
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Blue, R. Eric
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Roden, Christine
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Dundon, Samantha E.R.
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Rodríguez-Vargas, Anthony
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Jordan, Danielle C.
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Chen, Xiaomin
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Lyons, Shawn M.
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Crutchley, John M.
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Anderson, Paul
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Horb, Marko E.
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Gladfelter, Amy S.
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Giudice, Jimena
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https://hdl.handle.net/1912/25698As published
http://doi.org/10.1083/jcb.201911129DOI
10.1083/jcb.201911129Abstract
Fragile-X mental retardation autosomal homologue-1 (FXR1) is a muscle-enriched RNA-binding protein. FXR1 depletion is perinatally lethal in mice, Xenopus, and zebrafish; however, the mechanisms driving these phenotypes remain unclear. The FXR1 gene undergoes alternative splicing, producing multiple protein isoforms and mis-splicing has been implicated in disease. Furthermore, mutations that cause frameshifts in muscle-specific isoforms result in congenital multi-minicore myopathy. We observed that FXR1 alternative splicing is pronounced in the serine- and arginine-rich intrinsically disordered domain; these domains are known to promote biomolecular condensation. Here, we show that tissue-specific splicing of fxr1 is required for Xenopus development and alters the disordered domain of FXR1. FXR1 isoforms vary in the formation of RNA-dependent biomolecular condensates in cells and in vitro. This work shows that regulation of tissue-specific splicing can influence FXR1 condensates in muscle development and how mis-splicing promotes disease.
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© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Smith, J. A., Curry, E. G., Blue, R. E., Roden, C., Dundon, S. E. R., Rodríguez-Vargas, A., Jordan, D. C., Chen, X., Lyons, S. M., Crutchley, J., Anderson, P., Horb, M. E., Gladfelter, A. S., & Giudice, J. FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells. Journal of Cell Biology, 219(4), (2020): e201911129, doi: 10.1083/jcb.201911129.
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Smith, J. A., Curry, E. G., Blue, R. E., Roden, C., Dundon, S. E. R., Rodríguez-Vargas, A., Jordan, D. C., Chen, X., Lyons, S. M., Crutchley, J., Anderson, P., Horb, M. E., Gladfelter, A. S., & Giudice, J. (2020). FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells. Journal of Cell Biology, 219(4), e201911129.The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
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