Messenger (m)RNA export from the nucleus is essential for eukaryotic gene expression. Here, we identify a transcript-selective nuclear export mechanism affecting certain human transcripts, enriched for functions in genome duplication and repair, controlled by inositol polyphosphate multikinase (IPMK), an enzyme catalyzing inositol polyphosphate and phosphoinositide turnover. We studied transcripts encoding RAD51, a protein essential for DNA repair by homologous recombination (HR), to characterize the mechanism underlying IPMK-regulated mRNA export. IPMK depletion or catalytic inactivation selectively decreases the nuclear export of RAD51 mRNA, and RAD51 protein abundance, thereby impairing HR. Recognition of a sequence motif in the untranslated region of RAD51 transcripts by the mRNA export factor ALY requires IPMK. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), an IPMK product, restores ALY recognition in IPMK-depleted cell extracts, suggesting a mechanism underlying transcript selection. Our findings implicate IPMK in a transcript-selective mRNA export pathway controlled by phosphoinositide turnover that preserves genome integrity in humans.
Human inositol polyphosphate multikinase regulates transcript-selective nuclear mRNA export to preserve genome integrity.
Cell line
View SamplesWe sought to apply the technologies of gene expression profiling to detect genes significant in the aetiology of cervical carcinoma . We investigated 14 normal (NAD), 11 low grade squamous intrapepithelial lesions (LSIL), 21 high grade squamous intraepithelial lesions (HSIL) and 28 squamous cell carcinomas by Affymetrix GeneChip whole transcriptome profiling. Two SCC cell lines were also included in the cohort. Normal and SILS were profiled using the Affymetrix U133A platform, while SCCs and Cell lines were profiled using the Affymetrix U133A plus 2.0 array.
Gain and overexpression of the oncostatin M receptor occur frequently in cervical squamous cell carcinoma and are associated with adverse clinical outcome.
Specimen part, Cell line
View SamplesTo compare the transcriptome profiles of the two principal histological variants of malignant germ cell tumor that occur in childhood
Pediatric malignant germ cell tumors show characteristic transcriptome profiles.
No sample metadata fields
View SamplesComparison of miRNA expression profiles in malignant germ cell tumors compared to non-malignant control group.
Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets.
Sex, Age
View SamplesMicroarray was used to identify differential gene expression pattern in Barrett's esophagus (BE), compared to the normal adjacent epithelia gastric cardia (GC) and normal squamous esophagus (NE)
Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus.
Specimen part
View SamplesAlthough gain of chromosome-5p is one of the most frequent DNA copy number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross-sectional clinical study we showed that the microRNA processor Drosha (located on chromosome-5p) demonstrates frequent copy-number gain and over-expression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/over-expression experiments to demonstrate the functional significance of up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA-interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in eighteen cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi-resistant mutation. Forty-five microRNAs showed significant differential expression between the groups, including four of fourteen that were differentially-expressed in association with Drosha levels in clinical samples. miR-31 up-regulation in Drosha over-expressing samples/cell lines was the highest-ranked change (by adjusted p-value) in both analyses, an observation validated by Northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer-associated microRNAs that have the potential to regulate numerous protein-coding genes.
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sex, Cell line
View SamplesComparison of mRNA expression profiles in W12 Series 1 cervical ectokeratinocytes at passage number 22 versus 19 (during which time the cells gain an invasive phenotype)
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sex, Cell line
View SamplesUse traditional whole transcriptome profiling, and single cell whole transcriptome profiling to understand human pre-implantation development, undifferentiated human embryonic stem cells and differentiated human embryonic stem cells.
No associated publication
Sex, Age, Specimen part, Cell line, Treatment
View SamplesComparison of the changes in the gene expression profile of cells in which NF1 has been knocked down by RNAi in the presence/absence of the MEK inhibitor UO126
No associated publication
Specimen part
View SamplesWe used microarray to examine changes in gene expression in the absence of Csf1r in the brain and spleen.
Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the <i>Csf1r</i> Locus.
Sex
View Samples