Studying RNA–DNA interactome by Red-C identifies noncoding RNAs associated with various chromatin types and reveals transcription dynamics

Гаврилов, А. В.; Zharikova, Anastasia A.; Galitsyna, Aleksandra A.; Luzhin, Artem V; Rubanova, Natalia; Golov, Arkadiy K.; Petrova, Nadezhda V.; Logacheva, Maria D.; Kantidze, Omar L.; Ulianov, Sergey V.; Magnitov, Mikhail D.; Mironov, Andrey A.; Razin, Sergey V.

doi:10.1093/nar/gkaa457

Cited by 36 publications

(64 citation statements)

References 58 publications

(80 reference statements)

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“…Recently, a number of methods to detect genome-wide RNA-chromatin interactions were developed. However, one common feature of these methods (such as GRID-seq [ 35 ], MARGI [ 36 ], and Red-C [ 37 ]) was ligation of nearby DNA and RNA molecules using bridging oligonucleotides. The latter were in the range of ~4060 bases and could thus detect molecules separated by no more than 20nm given length of a nucleotide being 0.34nm.…”

Section: Resultsmentioning

confidence: 99%

“…Fourth, the RNA-chromatin interaction assay used in this study does not require direct interaction between lncRNAs and the target DNA, but rather relies on their relative proximity in the nucleus. Recently, a number of experimental approaches assaying either direct interactions or immediate proximity between DNA and RNA molecules genome-wide have been reported [ 35 37 ]. However, our results suggest that lncRNAs also engage in functionally important trans interactions that are more distal to their target genes yet still having impact on regulation of expression of these genes.…”

Section: Discussionmentioning

confidence: 99%

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Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans

Cao

Cai

et al. 2021

BMC Biol

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Background The majority of the human genome is transcribed in the form of long non-coding (lnc) RNAs. While these transcripts have attracted considerable interest, their molecular mechanisms of function and biological significance remain controversial. One of the main reasons behind this lies in the significant challenges posed by lncRNAs requiring the development of novel methods and concepts to unravel their functionality. Existing methods often lack cross-validation and independent confirmation by different methodologies and therefore leave significant ambiguity as to the authenticity of the outcomes. Nonetheless, despite all the caveats, it appears that lncRNAs may function, at least in part, by regulating other genes via chromatin interactions. Therefore, the function of a lncRNA could be inferred from the function of genes it regulates. In this work, we present a genome-wide functional annotation strategy for lncRNAs based on identification of their regulatory networks via the integration of three distinct types of approaches: co-expression analysis, mapping of lncRNA-chromatin interactions, and assaying molecular effects of lncRNA knockdowns obtained using an inducible and highly specific CRISPR/Cas13 system. Results We applied the strategy to annotate 407 very long intergenic non-coding (vlinc) RNAs belonging to a novel widespread subclass of lncRNAs. We show that vlincRNAs indeed appear to regulate multiple genes encoding proteins predominantly involved in RNA- and development-related functions, cell cycle, and cellular adhesion via a mechanism involving proximity between vlincRNAs and their targets in the nucleus. A typical vlincRNAs can be both a positive and negative regulator and regulate multiple genes both in trans and cis. Finally, we show vlincRNAs and their regulatory networks potentially represent novel components of DNA damage response and are functionally important for the ability of cancer cells to survive genotoxic stress. Conclusions This study provides strong evidence for the regulatory role of the vlincRNA class of lncRNAs and a potentially important role played by these transcripts in the hidden layer of RNA-based regulation in complex biological systems.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans

Cao

Cai

et al. 2021

BMC Biol

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“…MIREyA aims to easily find candidate activating miRNAs which trigger an enhancer and genes up-regulated by the enhancer. New emerging methods for studying RNA-DNA interactome detect previously unknown miRNAs bound to chromatin 40,41 which might be promising for further experimental investigation in terms of understanding complex gene regulation networks in detail. Although high-throughput data on RNA:DNA interactions in several cell types but not macrophages are available now, we could not confirm MiRNAs detected with MIREyA for Mtb infection using either RADICL-seq 41 or GRID-seq, 42 which is unsurprising since the ncRNA:DNA interactions are highly cell-type-specific.…”

Section: Discussionmentioning

confidence: 99%

MIREyA: a computational approach to detect miRNA-directed gene activation

et al. 2021

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Emerging studies demonstrate the ability of microRNAs (miRNAs) to activate genes via different mechanisms. Specifically, miRNAs may trigger an enhancer promoting chromatin remodelling in the enhancer region, thus activating the enhancer and its target genes. Here we present MIREyA, a pipeline developed to predict such miRNA-gene-enhancer trios based on an expression dataset which obviates the need to write custom scripts. We applied our pipeline to primary murine macrophages infected by Mycobacterium tuberculosis (HN878 strain) and detected Mir22, Mir221, Mir222, Mir155 and Mir1956, which could up-regulate genes related to immune responses. We believe that MIREyA is a useful tool for detecting putative miRNA-directed gene activation cases. MIREyA is available from: https://github.com/veania/MIREyA

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“…lncRNAs are involved in the formation of DNA loops and domains (Wang and Chang, 2011;Zhang et al, 2014), interchromosomal structures (Hacisuleyman et al, 2016), heterochromatic regions (Deng et al, 2009;Engreitz et al, 2013), subnuclear bodies (Mao et al, 2011), and the dynamic assembly of protein complexes (Tsai et al, 2010;Lin et al, 2014;Marín-Béjar et al, 2017). Several novel experimental methods allow the identification of lncRNAs binding to chromatin in vivo across the genome (Li et al, 2017;Sridhar et al, 2017;Bell et al, 2018;Bonetti et al, 2020;Gavrilov et al, 2020). Recruiting and binding to effector molecules is a prevalent mode of action of lncRNAs in both cis and trans activities.…”

Section: Signatures Of Conservation In Lncrnasmentioning

confidence: 99%

Evolution of Genome-Organizing Long Non-coding RNAs in Metazoans

Ramírez-Colmenero¹,

Oktaba

2020

Front. Genet.

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Long non-coding RNAs (lncRNAs) have important regulatory functions across eukarya. It is now clear that many of these functions are related to gene expression regulation through their capacity to recruit epigenetic modifiers and establish chromatin interactions. Several lncRNAs have been recently shown to participate in modulating chromatin within the spatial organization of the genome in the three-dimensional space of the nucleus. The identification of lncRNA candidates is challenging, as it is their functional characterization. Conservation signatures of lncRNAs are different from those of protein-coding genes, making identifying lncRNAs under selection a difficult task, and the homology between lncRNAs may not be readily apparent. Here, we review the evidence for these higher-order genome organization functions of lncRNAs in animals and the evolutionary signatures they display.

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Studying RNA–DNA interactome by Red-C identifies noncoding RNAs associated with various chromatin types and reveals transcription dynamics

Cited by 36 publications

References 58 publications

Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans

Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans

MIREyA: a computational approach to detect miRNA-directed gene activation

Evolution of Genome-Organizing Long Non-coding RNAs in Metazoans

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