Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Analysis of alternative exon-dependent interactome remodelling reveals multitasking functions of gene regulatory factors (iCLIP-Seq)

ABSTRACT: Alternative splicing is fundamental for the expansion of biological complexity, particularly in the vertebrate nervous system. Increasing evidence indicates that developmental stage and tissue-dependent alternative exons often control protein-protein interactions, yet only a minor fraction of these events has been characterized at the protein level. Using affinity purification-mass spectrometry (AP-MS) we show that approximately 60% of analyzed neural-differential exons in proteins previously implicated in transcriptional regulation result in the gain or loss of interaction partners. Focusing on Chtop and Sap30bp, the neural exons in these proteins unexpectedly remodel interactions with partners associated with mRNA processing and trafficking. Sap30bp additionally controls RNA localization by regulating the splicing of <100 nt ‘mini-introns’ that contribute to the nuclear retention of transcripts. These activities of Chtop and Sap30bp are linked to programs of transcriptomic regulation associated with development of the nervous system. AP-MS is thus a powerful approach for elucidating multifaceted functions of proteins imparted by context-dependent alternative exons.

ORGANISM(S): Mus musculus

PROVIDER: GSE224968 | GEO | 2023/11/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Analysis of alternative exon-dependent interactome remodelling reveals multitasking functions of gene regulatory factors (Sap30bp RNA-Seq)

Project description:Alternative splicing is fundamental for the expansion of biological complexity, particularly in the vertebrate nervous system. Increasing evidence indicates that developmental stage and tissue-dependent alternative exons often control protein-protein interactions, yet only a minor fraction of these events has been characterized at the protein level. Using affinity purification-mass spectrometry (AP-MS) we show that approximately 60% of analyzed neural-differential exons in proteins previously implicated in transcriptional regulation result in the gain or loss of interaction partners. Focusing on Chtop and Sap30bp, the neural exons in these proteins unexpectedly remodel interactions with partners associated with mRNA processing and trafficking. Sap30bp additionally controls RNA localization by regulating the splicing of <100 nt ‘mini-introns’ that contribute to the nuclear retention of transcripts. These activities of Chtop and Sap30bp are linked to programs of transcriptomic regulation associated with development of the nervous system. AP-MS is thus a powerful approach for elucidating multifaceted functions of proteins imparted by context-dependent alternative exons.

2023-11-24 | GSE224970 | GEO

Analysis of alternative exon-dependent interactome remodelling reveals multitasking functions of gene regulatory factors (Chtop RNA-Seq)

2023-11-24 | GSE224969 | GEO

Roth_Isoforms_BioID_Chtop_Sap30bp_VS31_VS33_2023_DIA

Project description:BioID data (DIA files) associated with the manuscript by Roth et al. 2023 describing the identification and characterization of neural alternative splicing events and associated PPI changes for 17 gene regulatory factors. BioID experiments were performed for two isoforms of Chtop and Sap30bp with/without a neural-regulated exon. For Chtop, cells were also treated with MS023, an arginine methyltransferase inhibitor, at 3 concentrations (DMSO, 1uM and 4uM).

2023-02-12 | MSV000091274 | MassIVE

Roth_Isoforms_BioID_Chtop_Sap30bp_VS30_VS32_2023_DDA

Project description:BioID data (DDA files) associated with the manuscript by Roth et al. 2023 describing the identification and characterization of neural alternative splicing events and associated PPI changes for 17 gene regulatory factors. BioID experiments were performed for two isoforms of Chtop and Sap30bp with/without inclusion of a neural-regulated exon. For Chtop, cells were also treated with MS023, an arginine methyltransferase inhibitor, at 3 concentrations (DMSO, 1uM and 4uM).

2023-02-16 | MSV000091298 | MassIVE

Regulation of Vertebrate Nervous System-Specific Alternative Splicing and Development by an SR-Related Protein

Project description:Alternative splicing is a key process underlying the evolution of increased proteomic and functional complexity and is especially prevalent in the mammalian nervous system. However, the factors and mechanisms governing nervous system-specific alternative splicing are not well understood. Through a genome-wide computational and expression profiling strategy, we have identified a tissue- and vertebrate-restricted Ser/Arg (SR)-repeat splicing factor, the neural-specific SR-related protein of 100 kDa (nSR100). We show that nSR100 regulates an extensive network of brain-specific alternative exons enriched in genes that function in neural cell differentiation. nSR100 acts by increasing the levels of the neural/brain-enriched polypyrimidine tract binding protein and by interacting with its target transcripts. Disruption of nSR100 prevents neural cell differentiation in cell culture and in the developing zebrafish. Our results thus reveal a critical neural-specific alternative splicing regulator, the evolution of which has contributed to increased complexity in the vertebrate nervous system. A microarray platform to profile alternative splicing levels for 8714 cassette-type alternative exons across a diverse spectrum of mouse tissues.

2010-05-15 | E-GEOD-16187 | biostudies-arrayexpress

Roth_Isoforms_FLAG_Chtop_Isoforms_MS023_VS35_2023_DDA

Project description:FLAG AP-MS data (DDA) associated with the manuscript by Roth et al. 2023 describing the identification and characterization of neural alternative splicing events and associated PPI changes for 17 gene regulatory factors. This dataset includes Chtop AP-MS data from N2a cells treated with and without the arginine methyltransferase inhibitor MS023.

2023-08-06 | MSV000092607 | MassIVE

Roth_Isoforms_FLAG_Chtop_Isoforms_MS023_VS34_2023_DIA

Project description:FLAG AP-MS data (DIA) associated with the manuscript by Roth et al. 2023 describing the identification and characterization of neural alternative splicing events and associated PPI changes for 17 gene regulatory factors. This dataset includes Chtop AP-MS data from N2a cells treated with and without the arginine methyltransferase inhibitor MS023.

2023-08-06 | MSV000092608 | MassIVE

Argonaute proteins couple chromatin silencing to alternative splicing (RNA IP-Seq)

Project description:While Argonaute (AGO) proteins play a major role in transcriptional gene silencing (TGS) in many organisms, their role in the nucleus of somatic mammalian cells remains elusive. Here, we have purified AGO1 and AGO2 chromatin-embedded complexes, and found these proteins associated with previously described partners, but also with chromatin modifiers and, rather unexpectedly, with different splicing factors. Using the CD44 gene as a model for alternative splicing, we show that both AGO1 and AGO2 are required for Protein Kinase C (PKC)-dependent variant exon inclusion. AGO proteins facilitate the spliceosome recruitment and modulate the elongation rate of RNA polymerase II (RNAPII). The recruitment of AGO proteins to CD44 transcribed region is dependent on both the endonuclease Dicer and the chromodomain-containing protein HP1g, and results in locally increased levels of histone H3 lysine 9 (H3K9) methylation on variant exons. Genome wide analysis of splicing in either AGO2 or Dicer null cells showed that the two proteins have similar effects on many splicing events. Finally, sRNAs associated with nuclear AGO2 are mostly in sense orientation relative to protein-coding genes, supporting a role for intragenic antisense non-coding RNAs in the recruitment AGO and splicing factors. Together, our data demonstrate for the first time that the endogenous RNAi pathway is involved in alternative splicing decisions, unravelling a new model in which AGO proteins couple RNAPII elongation and chromatin modification. Deep sequencing of small RNAs (approx. 15-80 nucleotides) bound to either cytoplasmic or chromatin-associated AGO2 complex.

2012-09-10 | E-GEOD-39748 | biostudies-arrayexpress

Functional coordination of alternative splicing in the mammalian central nervous system

Project description:Using a quantitative alternative splicing (AS) microarray platform, we have identified a large number of widely-expressed mouse genes containing single or coordinated-pairs of alternative exons that are spliced in a tissue-regulated fashion. The majority of these AS events display differential regulation in central nervous system (CNS) tissues. Approximately half of the corresponding genes have neural-specific functions and operate in common processes and interconnected pathways. Differential regulation of AS in the CNS tissues correlates strongly with a set of mostly new motifs that are predominantly located in the intron and constitutive exon sequences neighboring CNS-regulated alternative exons. Different subsets of these motifs are correlated with either increased inclusion or increased exclusion of alternative exons in CNS-tissues, relative to the other profiled tissues. Keywords: Alternative splicing

2007-08-01 | GSE8081 | GEO