A mutant syncytium with clustered nuclei can maintain normal growth and nucleocytoplasmic ratio control. As in the wild type, clustered nuclei exhibit cell cycle and transcriptional autonomy. Cyclin transcript enrichment near wild-type nuclei suggests a role in nuclear behavior; however, this spatial organization is dispensable for nuclear autonomy.
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.
Microtubules of the mitotic spindle direct cytokinesis in metazoans but this has not been documented in fungi. We report evidence that microtubule nucleators at the spindle pole body help coordinate cytokinetic furrow formation in fission yeast . The temperature-sensitive cps1-191 strain (Liu et al., 1999) with a D277N substitution in β-glucan synthase 1 (Cps1/Bgs1) was reported to arrest with an unconstricted contractile ring. We discovered that contractile rings in cps1-191 cells constrict slowly and that an mto2S338N mutation is required with the bgs1D277N mutation to reproduce the cps1-191 phenotype. Complexes of Mto2 and Mto1 with γ-tubulin regulate microtubule assembly. Deletion of Mto1 along with the bgs1D277N mutation also gives the cps1-191 phenotype, which is not observed in mto2S338N or mto1Δ cells expressing bgs1+. Both mto2S338N and mto1Δ cells nucleate fewer astral microtubules than normal and have higher levels of Rho1-GTP at the division site than wild-type cells. We report multiple conditions that sensitize mto1Δ and mto2S338N cells to furrow ingression phenotypes. [Media: see text]
Fragile-X mental retardation autosomal homolog-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 missplicing 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 intrinsicallydisordered 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 RNAdependent 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. KEYWORDS FXR1, alternative splicing, biomolecular condensation, myogenesis, Xenopus, muscle HIGHLIGHTS • The muscle-specific exon 15 impacts FXR1 functions • Alternative splicing of FXR1 is tissue-and developmental stage specific • FXR1 forms RNA-dependent condensates • Splicing regulation changes FXR1 condensate properties
Dundon and Pollard show that compromising the Mto1 or Mto2 regulators of the fission yeast γtubulin complex reduces or eliminates astral microtubules, exaggerates the effects of a non-lethal D277N substitution in β-glucan synthase 1 (Cps1/Bgs1) on the rate of cytokinetic furrow formation, and increases Rho-GTP at the cleavage site. AbstractMicrotubules of the mitotic spindle direct cytokinesis in metazoans but this has not been documented in fungi. We report evidence that astral microtubules help coordinate cytokinetic furrow formation in fission yeast. The temperature-sensitive cps1-191 strain (Liu et al., 1999) with a D277N substitution in β-glucan synthase 1 (Cps1/Bgs1) was reported to arrest with an unconstricted contractile ring. We discovered that rings in cps1-191 cells do constrict slowly and that an S338N mutation in the mto2 gene is required with the bgs1 D277N mutation to reproduce the cps1-191 phenotype. Complexes of Mto2 and Mto1 with γ-tubulin regulate microtubule assembly. Deletion of Mto1 along with the bgs1 D277N mutation also gives the cps1-191 phenotype, which is not observed in mto2 S338N or mto1Δ cells expressing bgs1 + . Both mto2 S338N and mto1Δ cells nucleate fewer astral microtubules than normal and have higher levels of Rho1-GTP at the division site than wild-type cells. We report multiple conditions that sensitize mto1Δ and mto2 S338N cells to furrow ingression phenotypes. (159 words)
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