Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inducible neuroblast differentiation into mature neurons reveals centrosome-spliceosome complex as a new splicing-modifying site

ABSTRACT: Nuclear transcriptional factors are key regulators of stem cell identity and differentiation, however whether extra-nuclear factors are involved in cell fate decisions remains unclear. Here we report that centrosome-associated spliceosome repression drives the differentiation of immature neuroblasts into neurons. Using neuroblastoma cells undergoing asymmetric division (ACD) as a model, we demonstrate that spliceosome components assemble preferentially at the mother centriole and undergo dynamic relocation in response to retinoic acid (RA) or centrosome ablation. ACD cells require selective Ninein splicing variants to promote the efficient formation of centrosome-associated spliceosome condensates. RA-induced neuron differentiation activates ciliogenesis and alternative splicing patterns, including cytoplasmic intron-retained transcripts in spliceosome-related genes. While pharmacological ablation of cilia impedes RA-dependent neuronal differentiation, inhibition of centriole duplication enhances synapse formation, recapitulating the molecular and morphological features of neurons. Mechanistically, centrosome repression-mediated differentiation of ACD cells into neurons relocates spliceosome factors between the nucleus and centrosome, activating cytoplasmic intron retention and exon inclusion in genes essential for ciliogenesis and cerebral cortical development. Collectively, our findings establish a cellular model for programmed splicing control and a strategy to enhance cytoplasmic spliced genes critical for human brain development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303693 | GEO | 2025/07/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The SON splicing factor is required for intracellular trafficking that promotes centriole assembly

Project description:Control of the number of centrosomes is critical for cell division, trafficking and cilia. Regulation of centrosome number occurs through the precise duplication of centrioles that reside in the center of centrosomes. Here we explored transcriptional control of centriole assembly by focusing on alternative splicing factors in isolation from other cell cycle processes. Of five splicing factors originally identified as required for centriole assembly, only SON is specifically required. Procentriole assembly is severely disrupted when SON is reduced but early centriole assembly events still occur. Whole genome mRNA sequencing identified thousands of genes whose splicing and expression are affected by the reduction of SON, with an enrichment of genes involved in the microtubule cytoskeleton. SON is required for the proper splicing and expression of the centriolar satellite protein, CEP131. Fluorescence microscopy and electron tomography establish key differences to the trafficking and microtubule network around the centrosomes that contribute to the centriole assembly defects. This establishes SON as required for centriole assembly, partially through its activity in splicing CEP131 and through control of microtubules organized by the centrosome.

2021-12-22 | GSE164278 | GEO

Inducible neuroblast differentiation into mature neurons reveals centrosome-spliceosome complex as a new splicing-modifying site

Project description:Inducible neuroblast differentiation into mature neurons reveals centrosome-spliceosome complex as a new splicing-modifying site

| PRJNA1297105 | ENA

Xenopus laevis

Project description:Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation.

| PRJNA147733 | ENA

CEP44 ensures the formation of bona fide centriole wall, a requirement for the centriole-to-centrosome conversion

Project description:The centriole-to-centrosome conversion is a mechanism of the centrosome maturation process that depends on the formation of a proper centriole wall structure. Beside the centriole wall biogenesis factors TUBD1 and TUBE1, CEP44 is involved in this process. Lack of CEP44 generates defects in the centriole wall structure and thus, it interferes with the centrosome maturation. POC1B was found to be an interactor of CEP44 in the immunoprecipitation and LC-MS experiment. The interaction and the function of this hit was validated with further independent biological experiments.

2020-03-24 | PXD017332 | Pride

The Unkempt RNA binding protein reveals a local translation program in centriole overduplication

Project description:Excess centrosomes cause defects in mitosis, cell-signaling, and cell migration, and therefore their assembly is tightly regulated. The divergent Polo kinase, PLK4, controls centriole duplication at the heart of centrosome assembly, and elevated PLK4 levels promote centrosome amplification (CA), a founding event of tumorigenesis. Here, we investigate the transcriptional consequences of elevated PLK4 and find Unkempt (UNK), a gene encoding an RNA binding protein with roles in mRNA translational regulation, to be one of only two upregulated mRNAs. UNK protein localizes to centrosomes and CEP131-positive centriolar satellites and promotes CEP131 localization to and around centrosomes. UNK's RNA binding activity is required for PLK4-induced centriole overduplication. Consistent with the loss in PLK4-induced centriole overduplication, UNK depletion disrupts PLK4 and centriole assembly protein localization. Finally, translation is enriched at centrosomes and centriolar satellites with UNK and CEP131 promoting this localized translation. In summary, UNK and CEP131 promote PLK4 localization and local translation at centrosomes during centriole overduplication.

2025-05-17 | GSE297133 | GEO

A ciliopathy complex restrains centriolar length and builds distal appendages to initiate ciliogenesis.

Project description:Mitosis segregates into each daughter cell two centrioles, the older of which is uniquely capable of generating a cilium. How this older centriole, called the mother centriole, initiates ciliogenesis remains poorly understood. We have identified an evolutionarily conserved complex comprised of CEP90, OFD1, MNR and FOPNL. Human mutations in CEP90, MNR and OFD1 cause ciliopathies. Super-resolution microscopy revealed that this complex forms a ring at the distal centriole. Centrioles of cells lacking MNR or CEP90 failed to assemble distal appendages and cannot generate cilia. In addition to the centrioles, complex members localized to centriolar satellites, proteinaceous granules surrounding the centrioles. Disruption of satellites did not affect distal appendage assembly, indicating that the centriolar pool is required for ciliogenesis. Consistent with an essential role in ciliogenesis, mice lacking MNR or CEP90 did not assemble cilia, did not survive beyond embryonic day 9.5, and did not transduce Hedgehog signals. In addition to ciliogenesis, MNR, but not CEP90, restrained centriolar length. MNR recruited both OFD1, required for centriolar length control, and CEP90, which recruits CEP83 to root distal appendages. Thus, an evolutionarily conserved ciliopathy-associated complex functions at the distal centriole to control centriole length and assemble distal appendages.

2021-06-15 | PXD022372 | Pride

Neuronal aging leads to disrupted RNA metabolism

Project description:Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged (i.e. >50 year-old) healthy donors directly into neurons, which retained their aging-associated phenotypes including senescence and dysregulation of CpG methylation. Here we show that aged neurons are broadly depleted of RNA-binding proteins, especially 26 spliceosome components. Intriguingly, splicing proteins – like the dementia and ALS-associated protein TDP-43 – mislocalize to the cytoplasm in aged neurons, which leads to widespread alternative splicing. Although spliceosome components can be sequestered within cytoplasmic stress granules, we find that aged neurons suffer from chronic stress that leads to the segregation of stress granule and spliceosome RNA-binding proteins. We link chronic stress to the accumulation of misfolded proteins and to poor HSP90α chaperone activity. Importantly, we also show that aged neurons respond poorly to acute stress treatments, leading to long-term retention of stress granules and failure to initiate transcription of stress-related heat shock proteins. Together our data demonstrates that dysregulation of RNA metabolism is a key driver of poor resiliency in aged neurons.

2025-02-19 | PXD055904 | Pride

Neuronal aging leads to disrupted RNA metabolism

2025-02-19 | PXD055825 | Pride

Neuronal aging leads to disrupted RNA metabolism

2025-02-19 | PXD055900 | Pride

Neuronal aging leads to disrupted RNA metabolism

2025-02-19 | PXD055826 | Pride