Noncoding Transcripts in Sense and Antisense Orientation Regulate the Epigenetic State of Ribosomal RNA Genes

Bierhoff, Holger; Schmitz, Kerstin Maike; Maass, Fabian; Ye, J.; Grummt, Ingrid

doi:10.1101/sqb.2010.75.060

Cited by 100 publications

(93 citation statements)

References 41 publications

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“…Coding genes could regulate lncRNAs, and vice versa ( Figure 7B). lncRNAs may be necessary to establish transcription by recruiting secondary mediators, as previously shown for the epigenetic state regulation of rRNA genes (52). In ChIRP experiments, we documented that the lncRNAs bound at the PTHLH and SOX9 loci.…”

Section: Discussionsupporting

confidence: 71%

A misplaced lncRNA causes brachydactyly in humans

Maass¹,

Rump²,

Schulz³

et al. 2012

J. Clin. Invest.

111

105

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Translocations are chromosomal rearrangements that are frequently associated with a variety of disease states and developmental disorders. We identified 2 families with brachydactyly type E (BDE) resulting from different translocations affecting chromosome 12p. Both translocations caused downregulation of the parathyroid hormone-like hormone (PTHLH) gene by disrupting the cis-regulatory landscape. Using chromosome conformation capturing, we identified a regulator on chromosome 12q that interacts in cis with PTHLH over a 24.4-megabase distance and in trans with the sex-determining region Y-box 9 (SOX9) gene on chromosome 17q. The element also harbored a long noncoding RNA (lncRNA). Silencing of the lncRNA, PTHLH, or SOX9 revealed a feedback mechanism involving an expression-dependent network in humans. In the BDE patients, the human lncRNA was upregulated by the disrupted chromosomal association. Moreover, the lncRNA occupancy at the PTHLH locus was reduced. Our results document what we believe to be a novel in cis-and in trans-acting DNA and lncRNA regulatory feedback element that is reciprocally regulated by coding genes. Furthermore, our findings provide a systematic and combinatorial view of how enhancers encoding lncRNAs may affect gene expression in normal development.

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Section: Discussionsupporting

confidence: 71%

A misplaced lncRNA causes brachydactyly in humans

Maass¹,

Rump²,

Schulz³

et al. 2012

J. Clin. Invest.

111

105

View full text Add to dashboard Cite

show abstract

“…The level of SUV4-20H2-catalyzed H4K20me3 is increased at rDNA regions during growth arrest in NIH 3T3 cells (80). PAPAS (promoter and prerRNA antisense) is a long noncoding RNA that is produced in an antisense orientation by RNA polymerase II (RNAPII) and covers sequences of the pre-rRNA coding region and the rDNA promoter (81). This noncoding RNA is upregulated in growtharrested cells and is accompanied by increased SUV4-20H2-mediated H4K20me3 and chromatin compaction (80,81).…”

Section: Involvement Of Histone Modifications In Rdna Silencing Histomentioning

confidence: 99%

“…PAPAS (promoter and prerRNA antisense) is a long noncoding RNA that is produced in an antisense orientation by RNA polymerase II (RNAPII) and covers sequences of the pre-rRNA coding region and the rDNA promoter (81). This noncoding RNA is upregulated in growtharrested cells and is accompanied by increased SUV4-20H2-mediated H4K20me3 and chromatin compaction (80,81). Additionally, PRMT5, the type II arginine methyltransferase that catalyzes monomethylation or symmetric dimethylation of histones H3 and H4, plays a key role in silencing rDNA when the cells are in a stationary or nonproliferating state (82).…”

Section: Involvement Of Histone Modifications In Rdna Silencing Histomentioning

confidence: 99%

The Epigenetic Pathways to Ribosomal DNA Silencing

Srivastava

Ahn

2016

Microbiol Mol Biol Rev

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SUMMARYHeterochromatin is the transcriptionally repressed portion of eukaryotic chromatin that maintains a condensed appearance throughout the cell cycle. At sites of ribosomal DNA (rDNA) heterochromatin, epigenetic states contribute to gene silencing and genome stability, which are required for proper chromosome segregation and a normal life span. Here, we focus on recent advances in the epigenetic regulation of rDNA silencing inSaccharomyces cerevisiaeand in mammals, including regulation by several histone modifications and several protein components associated with the inner nuclear membrane within the nucleolus. Finally, we discuss the perturbations of rDNA epigenetic pathways in regulating cellular aging and in causing various types of diseases.

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“…Previous studies revealed that rDNAs are transcribed bidirectionally in some organisms (Chekanova et al 2007;Bierhoff et al 2010), and that small RNAs can be produced from rDNA Pontes et al 2006;Lee et al 2009;Wei et al 2013). In flies, the involvement of the siRNA pathway in rDNA regulation was proposed because mutants in core RNAi factors, namely ago2 and dcr-2 mutants, exhibit rDNA phenotypes including aberrant nucleolar morphology, lower H3K9me2 occupancy at the rDNA loci and elevated extrachromosomal circular rDNA levels (Peng and Karpen 2007).…”

Section: Drosophila Rdna Generates Sirnasmentioning

confidence: 99%

“…In mice, noncoding transcripts from the IGS region regulate chromatin/DNA modification at the promoter region by recruiting the NoRC (nucleolar remodeling complex) (Mayer et al 2006). Furthermore, transcription of the antisense rDNA strand is often observed in a wide range of organisms and may also regulate rRNA biogenesis (Chekanova et al 2007;Bierhoff et al 2010). In Arabidopsis, a nuclear Argonaute AtAGO4 forms foci in nucleoli, and the formation of these foci is dependent on the siRNA pathway and 24-nt siRNAs produced from the pre-rRNA sequence Pontes et al 2006).…”

Section: Introductionmentioning

confidence: 99%

A deeply conserved, noncanonical miRNA hosted by ribosomal DNA

Chak

Mohammed

Lai

et al. 2015

RNA

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Advances in small RNA sequencing technologies and comparative genomics have fueled comprehensive microRNA (miRNA) gene annotations in humans and model organisms. Although new miRNAs continue to be discovered in recent years, these have universally been lowly expressed, recently evolved, and of debatable endogenous activity, leading to the general assumption that virtually all biologically important miRNAs have been identified. Here, we analyzed small RNAs that emanate from the highly repetitive rDNA arrays of Drosophila. In addition to endo-siRNAs derived from sense and antisense strands of the prerRNA sequence, we unexpectedly identified a novel, deeply conserved, noncanonical miRNA. Although this miRNA is widely expressed, this miRNA was not identified by previous studies due to bioinformatics filters removing such repetitive sequences. Deep-sequencing data provide clear evidence for specific processing with precisely defined 5 ′ and 3 ′ ends. Furthermore, we demonstrate that the mature miRNA species is incorporated in the effector complexes and has detectable trans regulatory activity. Processing of this miRNA requires Dicer-1, whereas the Drosha-Pasha complex is dispensable. The miRNA hairpin sequence is located in the internal transcribed spacer 1 region of rDNA and is highly conserved among Dipteran species that were separated from their common ancestor ∼100 million years ago. Our results suggest that biologically active miRNA genes may remain unidentified even in well-studied organisms.

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Noncoding Transcripts in Sense and Antisense Orientation Regulate the Epigenetic State of Ribosomal RNA Genes

Cited by 100 publications

References 41 publications

A misplaced lncRNA causes brachydactyly in humans

A misplaced lncRNA causes brachydactyly in humans

The Epigenetic Pathways to Ribosomal DNA Silencing

A deeply conserved, noncanonical miRNA hosted by ribosomal DNA

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