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E-MTAB-8037

ABSTRACT: Assessing the impact of XAB2 on gene expression and pre-mRNA splicing in mouse HEPA cells

PROVIDER: E-MTAB-8037 | ExpressionAtlas | 2020-12-09

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-MTAB-8037-analysis-methods.tsv	Tabular
	E-MTAB-8037-analytics.tsv	Tabular
	E-MTAB-8037-atlasExperimentSummary.Rdata	Rdata
	E-MTAB-8037-configuration.xml	Xml
	E-MTAB-8037-g2_g1-mvaPlot.png	Other

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E-MTAB-8035

Project description:The impact of XAB2 on gene expression and pre-mRNA splicing

2020-12-09 | E-MTAB-8035 | ExpressionAtlas

The impact of XAB2 on gene expression and pre-mRNA splicing

Project description:The impact of XAB2 on gene expression and pre-mRNA splicing

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Assessing the impact of XAB2 on gene expression and pre-mRNA splicing

Project description:Assessing the impact of XAB2 on gene expression and pre-mRNA splicing

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XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence

Project description:XAB2 is a multi-functional protein participating processes including transcription, splicing, DNA repair and mRNA export. Here we report POLR2A as a major target gene down-regulated after XAB2 depletion. XAB2 depletion led to severe splicing defects of POLR2A with significant intron retention. Such defects resulted in substantial loss of POLR2A at RNA and protein levels, which further impaired global transcription. Treatment of splicing inhibitor madrasin induced similar reduction of POLR2A. Screen using TMT identified several proteins involved in mRNA surveillance including Dom34 with elevated expression. Inhibition of translation or depletion of Dom34 rescued the expression of POLR2A by stabilizing its mRNA. Immuno-precipitation further confirmed that XAB2 associated with spliceosome components important to POLR2A expression. Domain mapping revealed that TPR motifs 2-4 and 11-12 of XAB2 were critical for POLR2A expression. Finally we showed POLR2A mediated cell senescence caused by XAB2 deficiency. Depletion of XAB2 or POLR2A induced cell senescence by up-regulation of p53 and p21, re-expression of POLR2A after XAB2 depletion alleviated cellular senescence. These data together support that XAB2 serves as a guardian of POLR2A expression to ensure global gene expression and antagonize cell senescence.

2019-11-13 | PXD012552 | Pride

Transcriptome-wide identification of splicing defects upon XAB2 knockdown

Project description:We performed RNA-seq to determine the impact of XAB2 depletion on global splicing. The results show that XAB2 depletion using two different siRNAs led to a wide range of splicing defects, with more than 50% events were intron retention.

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E-MTAB-4349

Project description:Gene expression analysis of SDH-deficient immortalized mouse kidney epithelial cells

2016-02-03 | E-MTAB-4349 | ExpressionAtlas

XAB2 involved in RNA processing.

Project description:RNA splicing and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice we show that XAB2, the human homologue of the yeast pre-mRNA-splicing factor SYF1 has a functional role in Nucleotide Excision Repair (NER) and the DNA damage response (DDR) in mammals. XAB2 interacts with spliceosome factors and is part of the core spliceosome that binds to spliceosomal U4 and U6 snRNAs during hepatic development. Ablation of XAB2 leads to defective NER, intron retention, the aberrant accumulation of pre-mRNAs and to a faulty ATM/ATR DDR signaling. Using functional approaches, we find that XAB2 dissociates from RNA targets upon persistent DNA damage or transcription blockage and from spliceosomal RNAs in the NER-defective developing livers. Thus, XAB2 functionally links NER to the spliceosomal response to DNA damage during hepatic development with important ramifications for transcription-coupled DNA repair disorders.

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E-GEOD-53894

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E-GEOD-50226

Project description:Gene expression data from 1833 cells and 1833 cells depleted of BACH1 mRNA expression

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