Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells

ABSTRACT: Different from canonical ubiquitin-like proteins, Hub1 does not form covalent conjugates with substrates but binds proteins non-covalently. In Saccharomyces cerevisiae, Hub1 associates with spliceosomes and mediates alternative splicing of SRC1, without affecting pre-mRNA splicing generally. Human Hub1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub1 binds to the spliceosomal protein Snu66 as in yeast, however, unlike its S. cerevisiae homolog, human Hub1 is essential for viability. Prolonged in vivo depletion of human Hub1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe and consequently cell death by apoptosis. Early consequences of Hub1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56878 | GEO | 2014/05/30

SECONDARY ACCESSION(S): PRJNA244855

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells

Project description:Different from canonical ubiquitin-like proteins, Hub1 does not form covalent conjugates with substrates but binds proteins non-covalently. In Saccharomyces cerevisiae, Hub1 associates with spliceosomes and mediates alternative splicing of SRC1, without affecting pre-mRNA splicing generally. Human Hub1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub1 binds to the spliceosomal protein Snu66 as in yeast, however, unlike its S. cerevisiae homolog, human Hub1 is essential for viability. Prolonged in vivo depletion of human Hub1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe and consequently cell death by apoptosis. Early consequences of Hub1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing. Human U2OS cells were transfected with siRNAs to specifically knockdown the ubiquitn-like protein Hub1. Cells treated with non-targeting oligos (GL2) served as negative control. Total RNAs of three biological replicates of each knockdown experiment were isolated and changes of splicing patterns were subsequently analyzed by Affymetrix GeneChip Human Exon 1.0 ST arrays

2014-05-30 | E-GEOD-56878 | biostudies-arrayexpress

Pre-mRNA splicing function of the ubiquitin-like protein Hub1/UBL-5 in Caenorhabditis elegans

Project description:The conserved ubiquitin-like protein Hub1/UBL-5 associates with proteins non-covalently. In yeast and human cells, Hub1 promotes splicing of precursor mRNAs with weak introns and alternative splicing, however, its splicing function has remained elusive in multicellular organisms. We demonstrate the splicing function of Hub1/UBL-5 in the free-living nematode Caenorhabditis elegans. UBL-5 binds to the HIND-containing splicing factors Snu66/SART-1 and PRP-38 and associates with other spliceosomal proteins. Caenorhabditis elegans hub1/ubl-5 mutants die at the larval L3 stage, and show accumulation of intron- and outron-containing transcripts. The latter observation adds to UBL-5’s splicing function in trans-RNA splicing. UBL-5 complements splicing defects of hub1-knockout Schizosaccharomyces pombe, confirming its functional conservation. Thus, UBL-5 is important for C. elegans development and cis- and trans-RNA splicing.

2024-05-21 | PXD033914 | Pride

UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells

Project description:UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions, our results show that UBL5 plays an evolutionary conserved role in pre-mRNA splicing, the integrity of which is essential for the fidelity of chromosome segregation. Total RNA was extracted from HeLa cells treated with control (CTRL), UBL5 (#57, #58, or #82), or SART1 siRNAs for 48 h and processed for RNA-Seq analysis

2014-08-05 | E-GEOD-59376 | biostudies-arrayexpress

UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells

2014-08-05 | GSE59376 | GEO

RNA-seq experiments from Saccharomyces cerevisiae overexpressing ubiquitin-related protein Hub1

Project description:We report introns more efficiently spliced in cells overexpressing ubiquitin-related protein Hub1

2017-06-01 | GSE84215 | GEO

Bacillus cereus HuB1-1

Project description:Bacillus cereus HuB1-1 Genome sequencing

| PRJNA70379 | ENA

Transcriptome analysis of khd1-1, spen3-1 and hub1-4 Arabidopsis mutants

Project description:HISTONE MONOUBIQUITINATION1 (HUB1) and its ortholog HUB2 regulate expression of genes involved in flowering, dormancy and circadian clock. HUB1 and HUB2 interact with two RNA-binding proteins KHD and SPEN. Phenotype analysis of the knock-down khd1-1, knock-out spen3-1, and knock-out hub mutants suggested that KHD and SPEN may contribute to flowering- and circadian clock-related functions that are also target of HUB1/2 activity. Transcriptome analysis was performed using RNA extracted from shoot apices of 10-day-old seedlings. After library preparation by TruSeq, RNA was sequenced on the Illumina HiSeq.

2018-05-14 | E-MTAB-6780 | biostudies-arrayexpress

kinetics of gene expression after light exposure in hub1-3 mutant compared to wild-type

Project description:au10-03_hub1 - kinetics of gene expression after light exposure in hub1-3 mutant compared to wild-type - Role of histone UbH2B in the regulation of gene expression in response to light - RNA from 5-day-old wild-type and hub1-3plants in 3 conditions were used for hybridization: 5 days of darkness, 5 days of darkness + 1 hour of light and 5 days of darkness + 6 hours of light. Keywords: genotype comparaison,time course

2011-05-20 | GSE21922 | GEO

Modeling of the U1 snRNP assembly pathway in alternative splicing in human cells using Petri nets

Project description:The investigation of spliceosomal processes is currently a topic of intense research in molecular biology. In the molecular mechanism of alternative splicing, a multi-protein–RNA complex – the spliceosome – plays a crucial role. To understand the biological processes of alternative splicing, it is essential to comprehend the biogenesis of the spliceosome. In this paper, we propose the first abstract model of the regulatory assembly pathway of the human spliceosomal subunit U1. Using Petri nets, we describe its highly ordered assembly that takes place in a stepwise manner.

2024-10-31 | MODEL2410300001 | BioModels

kinetics of gene expression after light exposure in hub1-3 mutant compared to wild-type

2011-05-20 | E-GEOD-21922 | biostudies-arrayexpress