Relationships between PROMPT and gene expression

Lloret-Llinares, Marta; Mapendano, Christophe K.; Martlev, Lasse H.; Lykke‐Andersen, Søren; Jensen, Torben Heick

doi:10.1080/15476286.2015.1109769

Cited by 30 publications

(26 citation statements)

References 29 publications

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“…This results in production of mitochondrial reactive oxygen species (mtROS) that hampers the RNA exosome activity first via oxidation of the subunits or via activation of stress-related kinases (24). Later, upon prolonged oxidative stress, transcription of RNA exosome subunits is turned down, possibly as a consequence of reduced TBP recruitment or increased DNA methylation at their promoters (45).…”

Section: Figure 4: Immune Cell Activation Results In the Production Omentioning

confidence: 99%

Reduced RNA turnover as a driver of cellular senescence

Mullani

Porozhan

Batsché

et al. 2019

Preprint

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Accumulation of senescent cells is an important contributor to chronic inflammation upon aging. While cytoplasmic DNA was shown to drive the inflammatory phenotype of senescent cells, an equivalent role for RNA has never been explored. Here, we show that cellular senescence correlates with reduced expression of RNA exosome subunits and coincident accumulation of promoter RNAs and immature RNA transcripts. Forced accumulation of these RNAs by inactivation of the Exosc3 exosome subunit induces expression of senescence markers and reduced mitochondrial gene expression. Reciprocally, mitochondrial suffering and oxidative stress results in reduced RNA decay, suggestive of a feedback loop between RNA decay and mitochondrial activity. As several of the accumulating RNAs are also produced during normal activation of immune cells and contain Alu sequences known to trigger an innate immune response, we propose that stabilizing immature and unstable RNAs participate in driving and maintaining the permanent inflammatory state characteristic of cellular senescence.

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Section: Figure 4: Immune Cell Activation Results In the Production Omentioning

confidence: 99%

Reduced RNA turnover as a driver of cellular senescence

Mullani

Porozhan

Batsché

et al. 2019

Preprint

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“…Indeed, we could observe at least twofold upregulation of 629 of the 1517 transcripts upregulated in HSV-1-infected cells, among them, e.g., BBC3as (Additional file 1 : Figure S2e). However, our antisense detection algorithm identified 12,417 antisense transcripts upregulated in EXOSC3-depleted cells compared to control cells, among them the recently described promoter upstream transcripts [ 23 , 24 ]. This discrepancy indicates that reduced exosome activity is unlikely a cause of the induction of antisense transcription by HSV-1 infection.…”

Section: Resultsmentioning

confidence: 99%

Widespread activation of antisense transcription of the host genome during herpes simplex virus 1 infection

et al. 2017

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BackgroundHerpesviruses can infect a wide range of animal species. Herpes simplex virus 1 (HSV-1) is one of the eight herpesviruses that can infect humans and is prevalent worldwide. Herpesviruses have evolved multiple ways to adapt the infected cells to their needs, but knowledge about these transcriptional and post-transcriptional modifications is sparse.ResultsHere, we show that HSV-1 induces the expression of about 1000 antisense transcripts from the human host cell genome. A subset of these is also activated by the closely related varicella zoster virus. Antisense transcripts originate either at gene promoters or within the gene body, and they show different susceptibility to the inhibition of early and immediate early viral gene expression. Overexpression of the major viral transcription factor ICP4 is sufficient to turn on a subset of antisense transcripts. Histone marks around transcription start sites of HSV-1-induced and constitutively transcribed antisense transcripts are highly similar, indicating that the genetic loci are already poised to transcribe these novel RNAs. Furthermore, an antisense transcript overlapping with the BBC3 gene (also known as PUMA) transcriptionally silences this potent inducer of apoptosis in cis.ConclusionsWe show for the first time that a virus induces widespread antisense transcription of the host cell genome. We provide evidence that HSV-1 uses this to downregulate a strong inducer of apoptosis. Our findings open new perspectives on global and specific alterations of host cell transcription by viruses.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1329-5) contains supplementary material, which is available to authorized users.

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“…FUS/TLS recruited to the CCND1 promoter through PROMPTs represses the histone acetyltransferase activity of CBP/p300, which results in decreased CCND1 transcription [ 154 ]. However, it seems that PROMPT-mediated gene regulation is not widespread, since no correlation was observed between altered expression of the downstream gene and increased PROMPT levels in DNA damage or Rrp40 depletion [ 155 ]. This might possibly indicate that most PROMPTs lack sequence elements necessary for recruiting specific RNA-binding proteins, and the action of only a small fraction of PROMPTs may be required for the DDR.…”

Section: Significance Of the Nuclear Rna Exosome In Mammalian Biolmentioning

confidence: 99%

RNA Surveillance by the Nuclear RNA Exosome: Mechanisms and Significance

Ogami

Chen

Manley

2018

ncRNA

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The nuclear RNA exosome is an essential and versatile machinery that regulates maturation and degradation of a huge plethora of RNA species. The past two decades have witnessed remarkable progress in understanding the whole picture of its RNA substrates and the structural basis of its functions. In addition to the exosome itself, recent studies focusing on associated co-factors have been elucidating how the exosome is directed towards specific substrates. Moreover, it has been gradually realized that loss-of-function of exosome subunits affect multiple biological processes such as the DNA damage response, R-loop resolution, maintenance of genome integrity, RNA export, translation and cell differentiation. In this review, we summarize the current knowledge of the mechanisms of nuclear exosome-mediated RNA metabolism and discuss their physiological significance.

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Relationships between PROMPT and gene expression

Cited by 30 publications

References 29 publications

Reduced RNA turnover as a driver of cellular senescence

Reduced RNA turnover as a driver of cellular senescence

Widespread activation of antisense transcription of the host genome during herpes simplex virus 1 infection

RNA Surveillance by the Nuclear RNA Exosome: Mechanisms and Significance

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