Long Noncoding RNAs Promote Transcriptional Poising of Inducible Genes

Cloutier, Sara C.; Wang, Siwen; Kit, Wai; Petell, Christopher J.; Tran, Elizabeth

doi:10.1371/journal.pbio.1001715

Cited by 45 publications

(61 citation statements)

References 80 publications

(185 reference statements)

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“…The FLO11 gene encodes a cell wall protein regulating adhesion between cells, and its expression is controlled by a pair of lncRNAs from the upstream region (24). lncRNAs have been proposed to regulate gene induction at the PHO5 (22) and GAL loci (21,52). A proposed mechanism involving transcriptional displacement of the Cyc8 repressor (20) is mechanistically similar to our model at HO.…”

Section: Discussionsupporting

confidence: 66%

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Disruption of promoter memory by synthesis of a long noncoding RNA

Yarrington

Chuong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The yeast HO endonuclease is expressed in late G1 in haploid mother cells to initiate mating-type interconversion. Cells can be arrested in G1 by nutrient deprivation or by pheromone exposure, but cells that resume cycling after nutrient deprivation or cyclindependent kinase (CDK) inactivation express HO in the first cell cycle, whereas HO is not expressed until the second cycle after release from pheromone arrest. Here, we show that transcription of a long noncoding RNA (lncRNA) mediates this differential response. The SBF and Mediator factors remain bound to the inactive promoter during arrest due to CDK inactivation, and these bound factors allow the cell to remember a transcriptional decision made before arrest. If the presence of mating pheromone indicates that this decision is no longer appropriate, a lncRNA originating at -2700 upstream of the HO gene is induced, and the transcription machinery displaces promoter-bound SBF, preventing HO transcription in the subsequent cell cycle. Further, we find that the displaced SBF is blocked from rebinding due to incorporation of its recognition sites within nucleosomes. Expressing the pHO-lncRNA in trans is ineffective, indicating that transcription in cis is required. Factor displacement during lncRNA transcription could be a general mechanism for regulating memory of previous events at promoters.lncRNA | nucleosomes | promoter memory | gene regulation | chromatin

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Section: Discussionsupporting

confidence: 66%

“…Long noncoding RNAs (lncRNAs) can regulate transcription (14)(15)(16)(17), and in budding yeast lncRNAs have been implicated in promoter regulation (18)(19)(20)(21)(22)(23)(24). Here we decipher the mechanism by which mating pheromone blocks expression of the HO endonuclease during the subsequent cell cycle.…”

Section: Significancementioning

confidence: 99%

Disruption of promoter memory by synthesis of a long noncoding RNA

Yarrington

Chuong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition to transcriptional repression, our group discovered that the GAL10 and GAL10s lncRNAs also function in transcriptional activation from transcriptionally repressive (Cglucose) to activating (¡galactose) conditions. 52 During this switch, the GAL lncRNAs enhance induction of the GAL protein coding genes from a repressed state by interfering with binding of the Tup1/Cyc8-corepressor complex. This occurs, presumably, by physical occlusion of the complex and results in derepression of the glucose-repressed GAL genes and allows for faster transcriptional activation in the presence of galactose (Fig.…”

mentioning

confidence: 99%

“…Interestingly, we found that cells lacking DBP2 display a much more rapid lncRNA-dependent transcriptional induction of the GAL genes, as well as reduced association of the Cyc8 corepressor. 52 This suggested that Dbp2 and/or its role in RNP assembly, antagonizes the transcriptionally activating role of the GAL lncRNAs and that dbp2D cells could be used as a tool to decipher the mechanism of transcriptional induction by these noncoding molecules.…”

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confidence: 99%

“…104 Repression DCI1 Fatty acid metabolism YES GAL10 lncRNA 47,48,105 Repression GAL genes Galactose metabolism YES GAL10/GAL10s lncRNAs. 52,53 Promotes induction GAL genes Galactose metabolism YES KCS1 lncRNAs 106 Translational interference KCS1 Inositol hexa/hepta bisphosphate kinase YES SUT719 30,35 Repression SUR7 Plasma membrane protein YES CDC28 AS RNA 29 Promotes induction CDC28 Cell cycle regulator NO RTL. 107 Repression Ty1 Retrotransposon NO ICR1.…”

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confidence: 99%

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LncRNAs: Bridging environmental sensing and gene expression

2016

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The survival of all organisms is dependent on complex, coordinated responses to environmental cues. Non-coding RNAs have been identified as major players in regulation of gene expression, with recent evidence supporting roles for long non-coding (lnc)RNAs in both transcriptional and post-transcriptional control. Evidence from our laboratory shows that lncRNAs have the ability to form hybridized structures called R-loops with specific DNA target sequences in S. cerevisiae, thereby modulating gene expression. In this Point of View, we provide an overview of the nature of lncRNA-mediated control of gene expression in the context of our studies using the GAL gene cluster as a model for controlling the timing of transcription.

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RNA helicase DEAD box protein 5 regulates Polycomb repressive complex 2/Hox transcript antisense intergenic RNA function in hepatitis B virus infection and hepatocarcinogenesis

et al. 2016

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Chronic hepatitis B virus (HBV) infection is a major factor in hepatocellular carcinoma (HCC) pathogenesis by a mechanism not yet understood. Elucidating mechanisms of HBV‐mediated hepatocarcinogenesis is needed to gain insights into classification and treatment of HCC. In HBV replicating cells, including virus‐associated HCCs, suppressor of zeste 12 homolog (SUZ12), a core subunit of Polycomb repressive complex2 (PRC2), undergoes proteasomal degradation. This process requires the long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR). Intriguingly, HOTAIR interacts with PRC2 and also binds RNA‐binding E3 ligases, serving as a ubiquitination scaffold. Herein, we identified the RNA helicase, DEAD box protein 5 (DDX5), as a regulator of SUZ12 stability and PRC2‐mediated gene repression, acting by regulating RNA‐protein complexes formed with HOTAIR. Specifically, knockdown of DDX5 and/or HOTAIR enabled reexpression of PRC2‐repressed genes epithelial cell adhesion molecule (EpCAM) and pluripotency genes. Also, knockdown of DDX5 enhanced transcription from the HBV minichromosome. The helicase activity of DDX5 stabilized SUZ12‐ and PRC2‐mediated gene silencing, by displacing the RNA‐binding E3 ligase, Mex‐3 RNA‐binding family member B (Mex3b), from HOTAIR. Conversely, ectopic expression of Mex3b ubiquitinated SUZ12, displaced DDX5 from HOTAIR, and induced SUZ12 down‐regulation. In G2 phase of cells expressing the HBV X protein (HBx), SUZ12 preferentially associated with Mex3b, but not DDX5, resulting in de‐repression of PRC2 targets, including EpCAM and pluripotency genes. Significantly, liver tumors from HBx/c‐myc bitransgenic mice and chronically HBV‐infected patients exhibited a strong negative correlation between DDX5 messenger RNA levels, pluripotency gene expression, and liver tumor differentiation. Notably, chronically infected HBV patients with HCC expressing reduced DDX5 exhibited poor prognosis after tumor resection, identifying DDX5 as an important player in poor prognosis HCC. Conclusion: The RNA helicase DDX5, and E3 ligase Mex3b, are important cellular targets for the design of novel, epigenetic therapies to combat HBV infection and poor prognosis HBV‐associated liver cancer. (Hepatology 2016;64:1033‐1048)

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Long Noncoding RNAs Promote Transcriptional Poising of Inducible Genes

Abstract: The GAL cluster-associated long non-coding RNAs (lncRNAs) promote rapid induction of GAL genes in budding yeast, thereby promoting a faster switch in transcriptional programs when needed.

Cited by 45 publications

References 80 publications

Disruption of promoter memory by synthesis of a long noncoding RNA

Disruption of promoter memory by synthesis of a long noncoding RNA

LncRNAs: Bridging environmental sensing and gene expression

RNA helicase DEAD box protein 5 regulates Polycomb repressive complex 2/Hox transcript antisense intergenic RNA function in hepatitis B virus infection and hepatocarcinogenesis

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