Expression data from glioblastoma stem cells after knockdown of PUS7
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE147382 | GEO | 2021/06/18
REPOSITORIES: GEO
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Project description:Pseudouridine is the first discovered and the most frequent modification in RNA. However, its biological functions in physiology and human diseases are largely unknown. Here, we show that pseudouridine synthase PUS7 is differentially expressed in glioblastoma patient tissues verse non-tumor brain tissues, and highly expressed in patient brain-derived cancer stem cells, compared to normal brain-derived neural stem cells. Upregulated expression of PUS7 predicts worse survival in glioblastoma patients in multiple databases. Indeed, we show that PUS7 plays an important role in regulating the self-renewal and tumorigenesis of glioblastoma stem cells. Overexpression of the wild type but not the catalytically inactive PUS7 increases the growth and self-renewal of GSCs. In contrast, knockdown of PUS7 dramatically suppresses GSC growth, self-renewal and tumorigenesis. Mechanistically, knockdown of PUS7 activates interferon pathway through translational control of TYK2 via PUS7-regulated tRNAs. Moreover, we have identified chemical inhibitors for PUS7 in this study. These chemical compounds target pseudouridine modification and suppress GSC growth and tumorigenesis, providing a potential therapeutic tool for GBM treatment.
2021-06-18 | GSE147342 | GEO
Project description:Pseudouridine (Ψ) is an abundant post-transcriptional modification found across all classes of RNA. Since its discovery in mRNAs a decade ago, it has been widely speculated that Y might govern additional post-transcriptional regulation of gene expression. Here, we demonstrate that one of the principal enzymes responsible for adding Y to mRNAs, pseudouridine synthase 7 (PUS7), accumulates in the cytoplasm under a variety of stress conditions in Saccharomyces cerevisiae and BEAS-2B human epithelial lung cells. The localization of PUS7 to the cytoplasm promotes Y-incorporation into hundreds of different mRNA sequences and increases cellular fitness under ROS and divalent metal ion stress. The preponderance of newly identified Y-sites lies within portions of the mRNA important for post-transcriptional control—-coding regions and 3’ UTRs. Quantitative proteomics reveal that shifts in the cellular post-transcriptional modification landscape upon PUS7 relocalization reshapes the proteome. Our data suggest a mechanism whereby stressors localize PUS7 in the cytoplasm to enable the direct modification and regulation of stress response mRNAs, thereby protecting cells from further stress-induced damage. (2A-PUS7-control682832B-PUS7-control682842C-PUS7-control682854A-PUS7-NES-Co682864A-PUS7-NES-Co682874B-PUS7-NES-Co682885A-PUS7-control-Co682895B-PUS7-control-Co682905C-PUS7-control-Co68291PUS7-NES_CU_1A 75059PUS7-NES_CU_1B 75060PUS7-NES_CU_1C 75061PUS7-NLS_CU_2A 75062PUS7-NLS_CU_2B 75063PUS7-NLS_CU_2C 75064PUS7-WT_CU_3A 75065PUS7-WT_CU_3B 75066PUS7-WT_CU_3C 75067)
2026-01-28 | PXD052684 | Pride
Project description:Pseudouridine is an abundant post-transcriptional modification found across all classes of RNA. Since its discovery in mRNAs a decade ago, it has been widely speculated that Y might govern additional post-transcriptional regulation of gene expression. Here, we demonstrate that one of the principal enzymes responsible for adding Y to mRNAs, pseudouridine synthase 7 (PUS7), accumulates in the cytoplasm under a variety of stress conditions in Saccharomyces cerevisiae and BEAS-2B human epithelial lung cells. The localization of PUS7 to the cytoplasm promotes Y-incorporation into hundreds of different mRNA sequences and increases cellular fitness under ROS and divalent metal ion stress. The preponderance of newly identified Y-sites lies within portions of the mRNA important for post-transcriptional control—-coding regions and 3’ UTRs. Quantitative proteomics reveal that shifts in the cellular post-transcriptional modification landscape upon PUS7 relocalization reshapes the proteome. Our data suggest a mechanism whereby stressors localize PUS7 in the cytoplasm to enable the direct modification and regulation of stress response mRNAs, thereby protecting cells from further stress-induced damage. (PUS7-NES_CU_1A 75059 PUS7-NES_CU_1B 75060 PUS7-NES_CU_1C 75061 PUS7-NLS_CU_2A 75062 PUS7-NLS_CU_2B 75063 PUS7-NLS_CU_2C 75064 PUS7-WT_CU_3A 75065 PUS7-WT_CU_3B 75066 PUS7-WT_CU_3C 75067))
2026-01-28 | PXD073675 | Pride
Project description:Expression data from glioblastoma stem cells after knockdown of PUS7
| PRJNA614467 | ENA
Project description:Background: Pulmonary hypertension (PH) is a life-threatening cardiovascular disorder characterized by irreversible pulmonary vascular remodeling and poor prognosis. RNA pseudouridylation, the most evolutionarily conserved RNA epigenetic modification, and its catalytic enzyme pseudouridine synthase 7 (PUS7) remained uncharacterized in PH, representing a major gap in understanding the epigenetic pathogenesis of the disease. Methods: We generated the first single-base resolution pseudouridine (Ψ) landscape in lung tissues of PH patients using bisulfite-induced deletion sequencing (BID-seq). PUS7 expression was analyzed in hypoxic pulmonary artery endothelial cells (PAECs), the lung tissues of PH patients, and Su5416-hypoxia rodent model. The functional roles of PUS7 were investigated through genetic manipulation (PUS7-deficiency cells, AAV-mediated overexpression, endothelial cell-specific knockdown, and heterozygous knockout mice) and pharmacological inhibition using NSC107512. Results: BID-seq revealed global Ψ dysregulation in the PH patient lung tissues. Among PUS family members, PUS7 was the most markedly upregulated in these tissues and in the hypoxic PAECs. Both gene knockdown and pharmacological inhibition with NSC107512 ameliorated PH, whereas AAV-mediated PUS7 overexpression exacerbated disease progression. RNA immunoprecipitation sequencing and mutagenesis studies demonstrated that PUS7 bound to and catalyzed Ψ at position 688 of Transforming Growth Factor Beta Induced Protein (TGFBI) mRNA, thereby stabilizing TGFBI and activating Phosphatidylinositol 3 Kinase (PI3K)-Protein Kinase B (AKT) signaling pathway. Furthermore, hypoxia-inducible factor 2α (HIF-2α) directly bound the PUS7 promoter, estabilishing a HIF-2α/PUS7/TGFBI/PI3K-AKT positive feedback loop that drives PH pathogenesis. Conclusions: PUS7-mediated pseudouridylation serves as a novel epigenetic driver of PH via the HIF-2α/PUS7/TGFBI/PI3K-AKT axis, positioning PUS7 as a promising therapeutic target for this devastating disease.
2026-07-07 | GSE334780 | GEO
Project description:Background: Pulmonary hypertension (PH) is a life-threatening cardiovascular disorder characterized by irreversible pulmonary vascular remodeling and poor prognosis. RNA pseudouridylation, the most evolutionarily conserved RNA epigenetic modification, and its catalytic enzyme pseudouridine synthase 7 (PUS7) remained uncharacterized in PH, representing a major gap in understanding the epigenetic pathogenesis of the disease. Methods: We generated the first single-base resolution pseudouridine (Ψ) landscape in lung tissues of PH patients using bisulfite-induced deletion sequencing (BID-seq). PUS7 expression was analyzed in hypoxic pulmonary artery endothelial cells (PAECs), the lung tissues of PH patients, and Su5416-hypoxia rodent model. The functional roles of PUS7 were investigated through genetic manipulation (PUS7-deficiency cells, AAV-mediated overexpression, endothelial cell-specific knockdown, and heterozygous knockout mice) and pharmacological inhibition using NSC107512. Results: BID-seq revealed global Ψ dysregulation in the PH patient lung tissues. Among PUS family members, PUS7 was the most markedly upregulated in these tissues and in the hypoxic PAECs. Both gene knockdown and pharmacological inhibition with NSC107512 ameliorated PH, whereas AAV-mediated PUS7 overexpression exacerbated disease progression. RNA immunoprecipitation sequencing and mutagenesis studies demonstrated that PUS7 bound to and catalyzed Ψ at position 688 of Transforming Growth Factor Beta Induced Protein (TGFBI) mRNA, thereby stabilizing TGFBI and activating Phosphatidylinositol 3 Kinase (PI3K)-Protein Kinase B (AKT) signaling pathway. Furthermore, hypoxia-inducible factor 2α (HIF-2α) directly bound the PUS7 promoter, estabilishing a HIF-2α/PUS7/TGFBI/PI3K-AKT positive feedback loop that drives PH pathogenesis. Conclusions: PUS7-mediated pseudouridylation serves as a novel epigenetic driver of PH via the HIF-2α/PUS7/TGFBI/PI3K-AKT axis, positioning PUS7 as a promising therapeutic target for this devastating disease.
2026-07-07 | GSE334990 | GEO
Project description:Background: Pulmonary hypertension (PH) is a life-threatening cardiovascular disorder characterized by irreversible pulmonary vascular remodeling and poor prognosis. RNA pseudouridylation, the most evolutionarily conserved RNA epigenetic modification, and its catalytic enzyme pseudouridine synthase 7 (PUS7) remained uncharacterized in PH, representing a major gap in understanding the epigenetic pathogenesis of the disease. Methods: We generated the first single-base resolution pseudouridine (Ψ) landscape in lung tissues of PH patients using bisulfite-induced deletion sequencing (BID-seq). PUS7 expression was analyzed in hypoxic pulmonary artery endothelial cells (PAECs), the lung tissues of PH patients, and Su5416-hypoxia rodent model. The functional roles of PUS7 were investigated through genetic manipulation (PUS7-deficiency cells, AAV-mediated overexpression, endothelial cell-specific knockdown, and heterozygous knockout mice) and pharmacological inhibition using NSC107512. Results: BID-seq revealed global Ψ dysregulation in the PH patient lung tissues. Among PUS family members, PUS7 was the most markedly upregulated in these tissues and in the hypoxic PAECs. Both gene knockdown and pharmacological inhibition with NSC107512 ameliorated PH, whereas AAV-mediated PUS7 overexpression exacerbated disease progression. RNA immunoprecipitation sequencing and mutagenesis studies demonstrated that PUS7 bound to and catalyzed Ψ at position 688 of Transforming Growth Factor Beta Induced Protein (TGFBI) mRNA, thereby stabilizing TGFBI and activating Phosphatidylinositol 3 Kinase (PI3K)-Protein Kinase B (AKT) signaling pathway. Furthermore, hypoxia-inducible factor 2α (HIF-2α) directly bound the PUS7 promoter, estabilishing a HIF-2α/PUS7/TGFBI/PI3K-AKT positive feedback loop that drives PH pathogenesis. Conclusions: PUS7-mediated pseudouridylation serves as a novel epigenetic driver of PH via the HIF-2α/PUS7/TGFBI/PI3K-AKT axis, positioning PUS7 as a promising therapeutic target for this devastating disease.
2026-07-07 | GSE335228 | GEO
Project description:Background: Pulmonary hypertension (PH) is a life-threatening cardiovascular disorder characterized by irreversible pulmonary vascular remodeling and poor prognosis. RNA pseudouridylation, the most evolutionarily conserved RNA epigenetic modification, and its catalytic enzyme pseudouridine synthase 7 (PUS7) remained uncharacterized in PH, representing a major gap in understanding the epigenetic pathogenesis of the disease. Methods: We generated the first single-base resolution pseudouridine (Ψ) landscape in lung tissues of PH patients using bisulfite-induced deletion sequencing (BID-seq). PUS7 expression was analyzed in hypoxic pulmonary artery endothelial cells (PAECs), the lung tissues of PH patients, and Su5416-hypoxia rodent model. The functional roles of PUS7 were investigated through genetic manipulation (PUS7-deficiency cells, AAV-mediated overexpression, endothelial cell-specific knockdown, and heterozygous knockout mice) and pharmacological inhibition using NSC107512. Results: BID-seq revealed global Ψ dysregulation in the PH patient lung tissues. Among PUS family members, PUS7 was the most markedly upregulated in these tissues and in the hypoxic PAECs. Both gene knockdown and pharmacological inhibition with NSC107512 ameliorated PH, whereas AAV-mediated PUS7 overexpression exacerbated disease progression. RNA immunoprecipitation sequencing and mutagenesis studies demonstrated that PUS7 bound to and catalyzed Ψ at position 688 of Transforming Growth Factor Beta Induced Protein (TGFBI) mRNA, thereby stabilizing TGFBI and activating Phosphatidylinositol 3 Kinase (PI3K)-Protein Kinase B (AKT) signaling pathway. Furthermore, hypoxia-inducible factor 2α (HIF-2α) directly bound the PUS7 promoter, estabilishing a HIF-2α/PUS7/TGFBI/PI3K-AKT positive feedback loop that drives PH pathogenesis. Conclusions: PUS7-mediated pseudouridylation serves as a novel epigenetic driver of PH via the HIF-2α/PUS7/TGFBI/PI3K-AKT axis, positioning PUS7 as a promising therapeutic target for this devastating disease.
2026-07-07 | GSE335339 | GEO
Project description:Pseudouridine (Ψ) is a widespread RNA modification in various RNA species, including rRNA, tRNA, snRNA and mRNA. Ψ plays a crucial role in RNA metabolism, where it regulates pre-mRNA splicing and affects protein translation. Whether and how Ψ may regulate transcription have not be adequately studied. Here, we report that pseudorudine synthase 7 (PUS7) can mediate pseudouridylation of 7SK small nuclear RNA (snRNA), a regulator of RNA polymerase II (Pol II) promoter-proximal pausing. PUS7 loss leads to hypo-pseudouridylation and facilitates sequestration of the positive transcription elongation factor b (P-TEFb) complex from 7SK. The release of P-TEFb from 7SK increases serine 2 phosphorylation (Ser2P) in the RNA Pol II C-terminal domain and enhances transcription elongation. In colorectal cancer (CRC) cells, the Ψ level of 7SK could be modulated by PUS7, or by site-specifically targeted pseudouridylation through dCas13b-guided system. Hypo-pseudouridylation on 7SK with PUS7 depletion promotes KLF6/DDIT3-mediated cell apoptosis and sensitizes CRC cells to 5-FU.
2025-09-09 | GSE288120 | GEO
Project description:Pseudouridylation (pseudouridine) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of pseudouridine remains poorly understood. Here, we show that a pseudouridine-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the pseudouridine ‘writer’ PUS7 modifies and activates a network of tRNA-derived fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translational regulation leading to high protein biosynthesis and abnormal germ layer specification. Dysregulation of PUS7 and tRFs in myeloid malignancies associates with altered translation rates, suggesting a role of pseudouridine in tumorigenesis. Our findings unveil a critical function of pseudouridine in directing translational control in stem cells with promisingly broad implications for human disease.
2018-04-09 | GSE101485 | GEO