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Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome

ABSTRACT: Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome

PROVIDER: PRJNA835865 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19128823.fastq.gz	Fastqsanger.gz
	SRR19128824.fastq.gz	Fastqsanger.gz
	SRR19128825.fastq.gz	Fastqsanger.gz
	SRR19128826.fastq.gz	Fastqsanger.gz
	SRR19128827.fastq.gz	Fastqsanger.gz

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Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome

Project description:In this study, we reveal insights into the biogenesis of downstream-of-gene (DoG)-containing RNAs in human cancers.

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Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome.

Project description:Downstream-of-gene (DoG) transcripts are an emerging class of noncoding RNAs. However, it remains largely unknown how DoG RNA production is regulated and whether alterations in DoG RNA signatures exist in major cancers. Here, through transcriptomic analyses of matched tumors and nonneoplastic tissues and cancer cell lines, we reveal a comprehensive catalog of DoG RNA signatures. Through separate lines of evidence, we support the biological importance of DoG RNAs in carcinogenesis. First, we show tissue-specific and stage-specific differential expression of DoG RNAs in tumors versus paired normal tissues with their respective host genes involved in tumor-promoting versus tumor-suppressor pathways. Second, we identify that differential DoG RNA expression is associated with poor patient survival. Third, we identify that DoG RNA induction is a consequence of treating colon cancer cells with the topoisomerase I (TOP1) poison camptothecin and following TOP1 depletion. Our results underlie the significance of DoG RNAs and TOP1-dependent regulation of DoG RNAs in diversifying and modulating the cancer transcriptome.

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TT-TL-seq reveals transcriptional profiles that accompany DoG induction after hyperosmotic stress.

Project description:TT-TimeLapse-seq was used to investigate the nascent transcription profiles that accompany the induction of downstream-of-gene (DoG) containing transcripts in human cell lines. Data from HEK-293T cells exposed to hyperosmotic stress and cells transfected with siRNAs against Integrator subunit 11 are included.

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Hyperosmotic stress induces downstream-of-gene transcription and alters the RNA Polymerase II interactome despite widespread transcriptional repression

Project description:Stress-induced readthrough transcription results in the synthesis of thousands of downstream-of-gene (DoG) containing transcripts. The mechanisms underlying DoG formation during cellular stress remain unknown. Nascent transcription profiles during DoG induction in human cell lines using TT-TimeLapse-seq revealed that hyperosmotic stress induces widespread transcriptional repression. Yet, DoGs are produced regardless of the transcriptional level of their upstream genes. ChIP-seq confirmed that the stress-induced redistribution of RNA Polymerase (Pol) II correlates with the transcriptional output of genes. Stress-induced alterations in the Pol II interactome are observed by mass spectrometry. While subunits of the cleavage and polyadenylation machinery remained Pol II-associated, Integrator complex subunits dissociated from Pol II under stress conditions. Depleting the catalytic subunit of the Integrator complex, Int11, using siRNAs induces hundreds of readthrough transcripts, whose parental genes partially overlap those of stress-induced DoGs. Our results provide insights into the mechanisms underlying DoG production and how Integrator activity influences DoG transcription. This SuperSeries is composed of the SubSeries listed below.

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Gene expression from beagle dog mandible

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