FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells.
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.
Duke Scholars
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- Young Adult
- Xenopus Proteins
- Xenopus
- RNA-Binding Proteins
- Muscles
- Muscle Development
- Muscle Cells
- Middle Aged
- Mice, Inbred Strains
- Mice, Inbred C57BL
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Location
Related Subject Headings
- Young Adult
- Xenopus Proteins
- Xenopus
- RNA-Binding Proteins
- Muscles
- Muscle Development
- Muscle Cells
- Middle Aged
- Mice, Inbred Strains
- Mice, Inbred C57BL