Antisense transcription licenses nascent transcripts to mediate transcriptional gene silencing

Dang, Yunkun; Chéng, Jiāsēn; Sun, Xiepeng; Zhou, Zhipeng; Liu, Yi

doi:10.1101/gad.285791.116

Cited by 20 publications

(13 citation statements)

References 67 publications

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“…It remains paradoxical that gene silencing induced by heterochromatin formation requires sRNA production via cotranscriptional processes, sometimes from lncRNAs ( 62 – 66 ). To search for any lncRNAs associated with sRNA-enriched loci that could be indicative of transcriptional gene silencing events, we examined the top 80 sRNA clusters ranked by the number of mapped reads, which accounted for 62% of mapped sRNA reads (see Table D in Text S1 ).…”

Section: Resultsmentioning

confidence: 99%

Developmental Dynamics of Long Noncoding RNA Expression during Sexual Fruiting Body Formation in Fusarium graminearum

Kim

Miguel-Rojas

Wang

et al. 2018

mBio

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Long noncoding RNA (lncRNA) plays important roles in sexual development in eukaryotes. In filamentous fungi, however, little is known about the expression and roles of lncRNAs during fruiting body formation. By profiling developmental transcriptomes during the life cycle of the plant-pathogenic fungus Fusarium graminearum, we identified 547 lncRNAs whose expression was highly dynamic, with about 40% peaking at the meiotic stage. Many lncRNAs were found to be antisense to mRNAs, forming 300 sense-antisense pairs. Although small RNAs were produced from these overlapping loci, antisense lncRNAs appeared not to be involved in gene silencing pathways. Genome-wide analysis of small RNA clusters identified many silenced loci at the meiotic stage. However, we found transcriptionally active small RNA clusters, many of which were associated with lncRNAs. Also, we observed that many antisense lncRNAs and their respective sense transcripts were induced in parallel as the fruiting bodies matured. The nonsense-mediated decay (NMD) pathway is known to determine the fates of lncRNAs as well as mRNAs. Thus, we analyzed mutants defective in NMD and identified a subset of lncRNAs that were induced during sexual development but suppressed by NMD during vegetative growth. These results highlight the developmental stage-specific nature and functional potential of lncRNA expression in shaping the fungal fruiting bodies and provide fundamental resources for studying sexual stage-induced lncRNAs.

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Section: Resultsmentioning

confidence: 99%

Developmental Dynamics of Long Noncoding RNA Expression during Sexual Fruiting Body Formation in Fusarium graminearum

Kim

Miguel-Rojas

Wang

et al. 2018

mBio

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“…First, tail-module dependent recruitment of Mediator to the Ty1 promoter could lead to enhanced Ty1 transcription, and this could repress the downstream Ty1i promoter by read-through effects. In this mechanism, the polymerase moving from the Ty1 TSS could disrupt transcription factor or PIC binding to the Ty1i promoter [ 66 – 68 ]. In the second mechanism, the Mediator tail could act as a direct repressor of the Ty1i promoter.…”

Section: Resultsmentioning

confidence: 99%

The Mediator co-activator complex regulates Ty1 retromobility by controlling the balance between Ty1i and Ty1 promoters

et al. 2018

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The Ty1 retrotransposons present in the genome of Saccharomyces cerevisiae belong to the large class of mobile genetic elements that replicate via an RNA intermediary and constitute a significant portion of most eukaryotic genomes. The retromobility of Ty1 is regulated by numerous host factors, including several subunits of the Mediator transcriptional co-activator complex. In spite of its known function in the nucleus, previous studies have implicated Mediator in the regulation of post-translational steps in Ty1 retromobility. To resolve this paradox, we systematically examined the effects of deleting non-essential Mediator subunits on the frequency of Ty1 retromobility and levels of retromobility intermediates. Our findings reveal that loss of distinct Mediator subunits alters Ty1 retromobility positively or negatively over a >10,000-fold range by regulating the ratio of an internal transcript, Ty1i, to the genomic Ty1 transcript. Ty1i RNA encodes a dominant negative inhibitor of Ty1 retromobility that blocks virus-like particle maturation and cDNA synthesis. These results resolve the conundrum of Mediator exerting sweeping control of Ty1 retromobility with only minor effects on the levels of Ty1 genomic RNA and the capsid protein, Gag. Since the majority of characterized intrinsic and extrinsic regulators of Ty1 retromobility do not appear to effect genomic Ty1 RNA levels, Mediator could play a central role in integrating signals that influence Ty1i expression to modulate retromobility.

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“…We considered the possibility that the novel methylation was directed by small interfering RNAs, such as Dicerindependent small interfering RNAs (disiRNAs) that have been implicated in low-level methylation associated with antisense or convergent transcription (Lee et al 2010;Dang et al 2016). To test this, we deleted the eri-1gene, which encodes the RNase necessary for disiRNA and disiRNA locus DNA methylation (Dang et al 2016). Loss of ERI-1 did not abolish the peaks of cytosine methylation that appear in dim-1 mutants ( Figure S7), ruling out this possibility.…”

Section: Hyper-methylation At Intergenic Regions In Dim-1 Strainsmentioning

confidence: 99%

Nucleosome Positioning by an Evolutionarily Conserved Chromatin Remodeler Prevents Aberrant DNA Methylation in Neurospora

et al. 2018

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In the filamentous fungus Neurospora crassa, constitutive heterochromatin is marked by tri-methylation of histone H3 lysine 9 (H3K9me3) and DNA methylation. We identified mutations in the Neurospora defective in methylation-1 (dim-1) gene that cause defects in cytosine methylation and implicate a putative AAA-ATPase chromatin remodeler. Although it was well-established that chromatin remodelers can affect transcription by influencing DNA accessibility with nucleosomes, little was known about the role of remodelers on chromatin that is normally not transcribed, including regions of constitutive heterochromatin. We found that dim-1 mutants display both reduced DNA methylation in heterochromatic regions as well as increased DNA methylation and H3K9me3 in some intergenic regions associated with highly expressed genes. Deletion of dim-1 leads to atypically spaced nucleosomes throughout the genome and numerous changes in gene expression. DIM-1 localizes to both heterochromatin and intergenic regions that become hyper-methylated in dim-1 strains. Our findings indicate that DIM-1 normally positions nucleosomes in both heterochromatin and euchromatin and that the standard arrangement and density of nucleosomes is required for the proper function of heterochromatin machinery.

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Antisense transcription licenses nascent transcripts to mediate transcriptional gene silencing

Cited by 20 publications

References 67 publications

Developmental Dynamics of Long Noncoding RNA Expression during Sexual Fruiting Body Formation in Fusarium graminearum

Developmental Dynamics of Long Noncoding RNA Expression during Sexual Fruiting Body Formation in Fusarium graminearum

The Mediator co-activator complex regulates Ty1 retromobility by controlling the balance between Ty1i and Ty1 promoters

Nucleosome Positioning by an Evolutionarily Conserved Chromatin Remodeler Prevents Aberrant DNA Methylation in Neurospora

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