| First Author | Smith JA | Year | 2020 |
| Journal | J Cell Biol | Volume | 219 |
| Issue | 4 | PubMed ID | 32328638 |
| Mgi Jnum | J:291328 | Mgi Id | MGI:6446543 |
| Doi | 10.1083/jcb.201911129 | Citation | Smith JA, et al. (2020) FXR1 splicing is important for muscle development and biomolecular condensates in muscle cells. J Cell Biol 219(4) |
| abstractText | 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. |
