FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells.
J Cell Biol
; 219(4)2020 04 06.
Article
in En
| MEDLINE
| ID: mdl-32328638
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA-Binding Proteins
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Alternative Splicing
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Xenopus Proteins
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Muscle Cells
Limits:
Adult
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Aged
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Animals
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Female
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Humans
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Infant
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Male
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Middle aged
Language:
En
Journal:
J Cell Biol
Year:
2020
Type:
Article