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Hypoxia-induced SETX links replication stress with the unfolded protein response

ABSTRACT: Hypoxia-induced SETX links replication stress with the unfolded protein response

PROVIDER: PRJNA661072 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12573869_1.fastq.gz	Fastqsanger.gz
	SRR12573869_2.fastq.gz	Fastqsanger.gz
	SRR12573870_1.fastq.gz	Fastqsanger.gz
	SRR12573870_2.fastq.gz	Fastqsanger.gz
	SRR12573871_1.fastq.gz	Fastqsanger.gz

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Hypoxia-induced SETX links replication stress with the unfolded protein response

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Hypoxia-induced SETX links replication stress with the unfolded protein response.

Project description:Tumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.

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GNL3/nucleostemin links DNA replication homeostasis and replication forks stability

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Epigenomic profiling of SETX in meiotic germ cells by ChIP-seq

Project description:SETX is a DNA/RNA helicase that resolves R-loop, and lack of SETX in germ cells causes meiotic arrest. To investigate roles of SETX in transcription during meiosis, we perfomred ChIP-seq of SETX using antibodies.

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Epigenomic profiling of SETX and Rloops in meiotic germ cells by CUT&Tag

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SETX attenuates the antiviral innate immune response and controls viral biogenesis (GRO-Seq)

Project description:The innate immune response is the first line of defense against pathogens, and factors that control this cellular response represent targets for treating both infectious and inflammatory diseases. Here, we reveal a novel role for the human helicase SETX, also previously implicated in amyotrophic lateral sclerosis (ALS4) and ataxia with oculomotor apraxia (AOA2), in controlling the magnitude of the antiviral response. Cells depleted for SETX and AOA2 patient-derived SETX-null cells show increased expression of antiviral mediators in response to infection. Mechanistically, this effect is achieved through SETX-mediated inhibition of RNAPII transcription of antiviral genes, and depends on SETX helicase activity. Our results suggest that SETX helps maintain the delicate balance between controlling viral infection and avoiding the potentially detrimental effects of an excessive antiviral response. More broadly, the observation that SETX can regulate the transcriptional activity of specific genes may have important implications for disorders where SETX function is compromised. A549 cells that were transfected with either control non-targeting or SETX-specific siRNAs were infected with the Influenza A virus (A/PR/8/34(ΔNS1) strain) at a multiplicity of infection (MOI) of 3 for 4 hours. Nuclei were then extracted and used to prepare Global Run-On Sequencing (GRO-seq) libraries.

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Gene expression profiling in Setx shRNA P19 cells, wild type human Setx P19 transfected cells with and without retionoic acid

Project description:Analysis of senataxin effect on neuronal differentiation and neurite growth in RA-treated P19 cells by modulating senataxin expression levels. Senataxin silencing does not grossly affect the gene expression profiles of P19 cells At day one total RNA from Setx shRNA P19 cells, wild type human Setx P19 transfected cells with and without retionoic acid were used to compare gene expression profiling versus P19 control cells

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RNA-seq of Setx KI and WT Spinal Cord

Project description:The goal of this study is to compare differences in splicing between bulk spinal cord samples isolated from Setx KI and WT mice

2022-04-22 | GSE199664 | GEO

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