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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

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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

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

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

Bacillus cereus HuB1-1

Project description:Bacillus cereus HuB1-1 Genome sequencing

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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

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

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

H3K4me3 profiling in HUB1 Arabidopsis mutant seedlings

Project description:The functional determinants of histone H3 Lys-4 trimethylation (H3K4me3), their potential dependency on histone H2B monoubiquitination (H2Bub) and their contribution in defining gene expression programs are poorly defined in plant systems. Differently from S. cerevisiae in which a single SET1 protein catalyzes H3 Lys-4 trimethylation as part of COMPASS (COMPlex of proteins ASsociated with SET1), this activity involves multiple histone methyltransferases (HMTs) in Arabidopsis thaliana, among which the plant-specific SDG2 (SET DOMAIN GROUP2) has a prominent role. Here we report that SDG2 co-regulates hundreds genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of the evolutionarily conserved COMPASS complex. Accordingly, S2Lb associates with the AtCOMPASS core subunit WDR5a within a high-molecular weight complex and is required for proper H3K4me3 enrichment over genes highly occupied by RNA Polymerase II. S2Lb knock-out plants display little transcriptomic defects, suggesting that H3K4me3 deposition is important for optimal gene induction rather than for determining on/off transcriptional states. We further report that S2Lb and H3K4me3 are accurately targeted over most genes in hub1 mutant plants lacking histone H2B monoubiquitination. Collectively, our study indicates that a plant-specific COMPASS-like complex acting mainly through an H2Bub-independent mechanism is a major determinant of H3K4me3 deposition in Arabidopsis.

2019-05-04 | GSE124296 | GEO

Saccharomyces cerevisiae

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

| PRJNA328390 | ENA