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Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression

ABSTRACT: Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression

PROVIDER: PRJNA1098000 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28597500.fastq.gz	Fastqsanger.gz
	SRR28597501.fastq.gz	Fastqsanger.gz
	SRR28597502.fastq.gz	Fastqsanger.gz
	SRR28597497.fastq.gz	Fastqsanger.gz
	SRR28597498.fastq.gz	Fastqsanger.gz

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Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression [PNUTS]

Project description:Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression [PNUTS]

| PRJNA1099143 | ENA

Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression [PNUTS]

Project description:Age-related diseases pose great challenges to health care systems worldwide. During aging, endothelial senescence increases the risk for cardiovascular disease. Recently, it was described that Phosphatase 1 Nuclear Targeting Subunit (PNUTS) has a central role in cardiomyocyte aging and homeostasis. Here, we determined the role of PNUTS in endothelial cell aging. We confirmed that PNUTS is repressed in senescent endothelial cells (ECs). Moreover, PNUTS silencing elicits several of the hallmarks of endothelial aging: senescence, reduced angiogenesis and loss of barrier function. To validate our findings in vivo, we generated an endothelial-specific inducible PNUTS-deficient mouse line (Cdh5-CreERT2;PNUTSfl/fl), termed PNUTSEC-KO. Two weeks after PNUTS deletion, PNUTSEC-KO mice presented severe multiorgan failure and vascular leakage. Transcriptomic analysis of PNUTS-silenced HUVECs and lungs of PNUTSEC-KO mice revealed that the PNUTS-PP1 axis tightly regulates the expression of semaphorin 3B (SEMA3B). Indeed, silencing of SEMA3B completely restored barrier function after PNUTS loss-of-function. These results reveal a pivotal role for PNUTS in endothelial homeostasis through a SEMA3B downstream pathway that provides a potential target against the effects of aging in ECs.

2024-04-15 | GSE263742 | GEO

Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression

2024-04-14 | GSE263531 | GEO

The PNUTS-protein phosphatase 1 complex acts as an intrinsic barrier to KSHV replication [eCLIP]

Project description:Control of RNA Polymerase II (pol II) elongation is a critical component of gene expression in mammalian cells. The PNUTS-protein phosphatase 1 (PP1) complex controls elongation rates, slowing pol II after polyadenylation sites to promote termination. The Kaposi's sarcoma-associated herpesvirus (KSHV) co-opts pol II to express its genes, but little is known about its regulation of pol II elongation. We identified PNUTS as a suppressor of a KSHV reporter gene in a genome-wide CRISPR screen. PNUTS depletion also enhances global KSHV gene expression and overall viral replication. Reflecting its host gene activities, PNUTS binds viral RNAs downstream of polyadenylation sites, restricts transcription readthrough of viral genes, and requires PP1 interaction. Surprisingly, PNUTS represses the KSHV reporter by decreasing productive elongation at the 5´-end of the gene. From these data, we conclude that PNUTS' activity forms an intrinsic barrier to KSHV replication likely by suppressing pol II elongation at promoter-proximal regions.

2022-11-19 | GSE201045 | GEO

The PNUTS-protein phosphatase 1 complex acts as an intrinsic barrier to KSHV replication [CRISPR]

2022-11-19 | GSE200991 | GEO

The PNUTS-protein phosphatase 1 complex acts as an intrinsic barrier to KSHV replication [RNA-seq]

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The PNUTS-protein phosphatase 1 complex acts as an intrinsic barrier to KSHV replication [ChIP-seq]

2022-11-19 | GSE200992 | GEO

The PNUTS-protein phosphatase 1 complex acts as an intrinsic barrier to KSHV replication [ChIP-Seq II]

Project description:In this study, we found that the host protein PNUTS suppressed Kaposi's sarcoma-associated herpesvirus (KSHV) gene expression during lytic reactivation and from heterologous viral reporters. To gain insights into the mechanism, we performed ChIP-seq of the pol II subunit RPB3 in cells with an integrated reporter containing the KSHV ORF59 gene. Our results were consistent with previous reports showing that depletion of PNUTS leads to global loss of pol II slow down and termination after polyadenylation sites. In contrast, PNUTS depletion appeared to decrease promoter-proximal pausing on our integrated reporter suggesting a distinct mode of gene regulation on viral genes.

2022-11-22 | GSE215345 | GEO

BRCA1 maintains telomere integrity through suppression of TERRA RNA and TERRA R-loop-induced DNA damage

Project description:Data in support of Vohhodina et al. "BRCA1 maintains telomere integrity through suppression of TERRA RNA and TERRA R-loop-induced DNA damage"

2021-04-21 | MSV000087276 | MassIVE

Tmprss2 maintains epithelial barrier integrity and transepithelial sodium transport

Project description:Tmprss2 maintains epithelial barrier integrity and transepithelial sodium transport

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