Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability

Rom, Aviv; Melamed, Liliya; Gil, Noa; Goldrich, Micah Jonathan; Kadir, Rotem; Golan, Matan; Biton, Inbal E.; Perry, Rotem Ben-Tov; Ulitsky, Igor

doi:10.1038/s41467-019-13075-8

Cited by 90 publications

(94 citation statements)

References 79 publications

(86 reference statements)

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“…In addition to Kcnq1ot1, we identified several other lncRNAs that demarcate specific nuclear compartments around their transcriptional loci containing their functional targets. For example: (i) Airn localizes within a TAD containing its reported imprinted target genes [110][111][112] Figure 7F) and has been shown to repress Chd2 expression 114,115 .…”

Section: Non-coding Rnas Guide Regulatory Proteins To Nuclear Compartmentioning

confidence: 99%

RNA promotes the formation of spatial compartments in the nucleus

Quinodoz

Bhat

Ollikainen

et al. 2020

Preprint

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The nucleus is a highly organized arrangement of RNA, DNA, and protein molecules that are compartmentalized within three-dimensional (3D) structures involved in shared functional and regulatory processes. Although RNA has long been proposed to play a global role in organizing nuclear structure, exploring the role of RNA in shaping nuclear structure has remained a challenge because no existing methods can simultaneously measure RNA-RNA, RNA-DNA, and DNA-DNA contacts within 3D structures. To address this, we developed RNA & DNA SPRITE (RD-SPRITE) to comprehensively map the location of all RNAs relative to DNA and other RNAs. Using this approach, we identify many RNAs that are localized near their transcriptional loci (RNA-DNA) together with other diffusible ncRNAs (RNA-RNA) within higher-order DNA structures (DNA-DNA). These RNA-chromatin compartments span three major classes of nuclear functions: RNA processing (including ribosome biogenesis, mRNA splicing, snRNA biogenesis, and histone mRNA processing), heterochromatin assembly, and gene regulation. More generally, we identify hundreds of ncRNAs that form stable nuclear compartments in spatial proximity to their transcriptional loci. We find that dozens of nuclear compartments require RNA to guide protein regulators into these 3D structures, and focusing on several ncRNAs, we show that these ncRNAs specifically regulate heterochromatin assembly and the expression of genes contained within these compartments. Together, our results demonstrate a unique mechanism by which RNA acts to shape nuclear structure by forming high concentration territories immediately upon transcription, binding to diffusible regulators, and guiding them into spatial compartments to regulate a wide range of essential nuclear functions.

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Section: Non-coding Rnas Guide Regulatory Proteins To Nuclear Compartmentioning

confidence: 99%

RNA promotes the formation of spatial compartments in the nucleus

Quinodoz

Bhat

Ollikainen

et al. 2020

Preprint

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“…In order to test the ability of LncLOOM to identify conserved modules in sequences that are not amenable for BLAST comparison, we focused on CHASERR , a lncRNA that we recently characterized as being essential for mouse viability [ 28 ]. CHASERR homologs are readily identifiable in different species based on the close proximity (< 2 kb) to the transcription start site of CHD2, as well as their characteristic 5-exon gene architecture [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences

et al. 2021

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Background Animal genomes contain thousands of long noncoding RNA (lncRNA) genes, a growing subset of which are thought to be functionally important. This functionality is often mediated by short sequence elements scattered throughout the RNA sequence that correspond to binding sites for small RNAs and RNA binding proteins. Throughout vertebrate evolution, the sequences of lncRNA genes changed extensively, so that it is often impossible to obtain significant alignments between sequences of lncRNAs from evolutionary distant species, even when synteny is evident. This often prohibits identifying conserved lncRNAs that are likely to be functional or prioritizing constrained regions for experimental interrogation. Results We introduce here LncLOOM, a novel algorithmic framework for the discovery and evaluation of syntenic combinations of short motifs. LncLOOM is based on a graph representation of the input sequences and uses integer linear programming to efficiently compare dozens of sequences that have thousands of bases each and to evaluate the significance of the recovered motifs. We show that LncLOOM is capable of identifying specific, biologically relevant motifs which are conserved throughout vertebrates and beyond in lncRNAs and 3′UTRs, including novel functional RNA elements in the CHASERR lncRNA that are required for regulation of CHD2 expression. Conclusions We expect that LncLOOM will become a broadly used approach for the discovery of functionally relevant elements in the noncoding genome.

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“…Another good example is the Chaserr lncRNA locus, which lies 16 kb upstream of the Chd2 protein- coding gene ( Rom et al, 2019 ). Although, knock-down of Chaserr RNA does cause a slight increase in Chd2 expression, additional lines of evidence infer that the transcription of the lncRNA gene is likely the most important function of Chaserr in regulating Chd2 ( Figure 4 ).…”

Section: Lncrna Genes In the Genomementioning

confidence: 99%

Beyond the RNA-dependent function of LncRNA genes

Ali

Grote

2020

eLife

180

116

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While long non-coding RNA (lncRNA) genes have attracted a lot of attention in the last decade, the focus regarding their mechanisms of action has been primarily on the RNA product of these genes. Recent work on several lncRNAs genes demonstrates that not only is the produced RNA species important, but also that transcription of the lncRNA locus alone can have regulatory functions. Like the functions of lncRNA transcripts, the mechanisms that underlie these genome-based functions are varied. Here we highlight some of these examples and provide an outlook on how the functional mechanisms of a lncRNA gene can be determined.

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Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability

Cited by 90 publications

References 79 publications

RNA promotes the formation of spatial compartments in the nucleus

RNA promotes the formation of spatial compartments in the nucleus

Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences

Beyond the RNA-dependent function of LncRNA genes

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