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Long noncoding RNAs in DNA methylation: new players stepping into the old game.

Zhao Y, Sun H, Wang H - Cell Biosci (2016)

Bottom Line: Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level.Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation.Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).

View Article: PubMed Central - PubMed

Affiliation: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT
Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level. Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation. Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).

No MeSH data available.


Related in: MedlinePlus

Genomic context and mechanisms of action of lncRNAs. a LncRNAs can be categorized according to their genomic loci relative to protein-coding genes. Intergenic lncRNAs (lincRNAs) are separate transcription units from protein-coding genes. Among them, a class may be transcribed from enhancers (eRNAs). Intronic lncRNAs are generated from the introns of protein-coding genes without overlapping with exons. Antisense lncRNAs are transcribed in opposite direction of protein-coding genes and overlap with the exons. Divergent lncRNAs are normally initiated from the promoter region of protein-coding genes. b LncRNAs exploit distinct mechanisms to elicit their regulatory roles in gene expression. ① lncRNAs can recruit proteins such as chromatin modifiers to target DNA; ② lncRNAs may act as decoy to titrate away DNA binding proteins like transcription factors; ③ lncRNAs can function as scaffold to bring multiple proteins into a complex; ④ to organize higher-order nuclear structure; ⑤ eRNAs can interact with Mediator and/or Cohesin complex to mediate and/or stabilize chromosomal looping between enhancers and cognate promoters. In cytoplasm, ⑥ lncRNAs can influence translation through intervening the loading of polysomes to mRNAs; ⑦ lncRNAs can serve as miRNA sponges to release their inhibitory roles on target mRNAs; ⑧ lncRNAs can regulate mRNA decay pathway, stabilizing or destabilizing mRNAs through RNA/RNA interaction with mRNA
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Fig1: Genomic context and mechanisms of action of lncRNAs. a LncRNAs can be categorized according to their genomic loci relative to protein-coding genes. Intergenic lncRNAs (lincRNAs) are separate transcription units from protein-coding genes. Among them, a class may be transcribed from enhancers (eRNAs). Intronic lncRNAs are generated from the introns of protein-coding genes without overlapping with exons. Antisense lncRNAs are transcribed in opposite direction of protein-coding genes and overlap with the exons. Divergent lncRNAs are normally initiated from the promoter region of protein-coding genes. b LncRNAs exploit distinct mechanisms to elicit their regulatory roles in gene expression. ① lncRNAs can recruit proteins such as chromatin modifiers to target DNA; ② lncRNAs may act as decoy to titrate away DNA binding proteins like transcription factors; ③ lncRNAs can function as scaffold to bring multiple proteins into a complex; ④ to organize higher-order nuclear structure; ⑤ eRNAs can interact with Mediator and/or Cohesin complex to mediate and/or stabilize chromosomal looping between enhancers and cognate promoters. In cytoplasm, ⑥ lncRNAs can influence translation through intervening the loading of polysomes to mRNAs; ⑦ lncRNAs can serve as miRNA sponges to release their inhibitory roles on target mRNAs; ⑧ lncRNAs can regulate mRNA decay pathway, stabilizing or destabilizing mRNAs through RNA/RNA interaction with mRNA

Mentions: A major advance in molecular biology over the past two decades has been the discovery and characterization of function for lncRNAs. The extraordinary maturation in sequencing technology, allowing the detection of low abundance transcripts in genome-wide transcriptomes analyses via massive parallel sequencing, has revealed significant levels of transcriptional activity within the unannotated and annotated regions of genome. Among many of the newly discovered non-coding transcripts, lncRNAs are the transcripts with a length over 200 nt, normally poorly conserved and do not serve as the templates for protein synthesis [16–19]. According to their genomic loci relative to protein-coding counterparts, lncRNAs can be further categorized as long intergenic ncRNAs (lincRNAs), antisense lncRNAs and intronic lncRNAs (Fig. 1) [16, 17]. Many of them are capped, spliced and polyadenylated similar to mRNAs. Recently, another class of lncRNAs, termed enhancer RNAs (eRNAs) generated from regulatory regions of genome, is emerging as important players in transcriptional activation of target mRNAs [20–22]. However, they are normally not spliced or polyadenylated. LncRNAs have been implicated in playing essential roles in every aspect of cellular processes and regulate gene expressions at different levels including chromatin organization, transcriptional control and post-transcriptional regulation (Fig. 1) [17]. The function of lncRNAs cannot currently be predicted from sequence information alone. An emerging theme, however, is the capacity of lncRNAs to modulate gene expression, with many of them participating in epigenetic control through interacting with various types of proteins involved in histone modification or chromatin remodeling. In particular, the Polycomb Repressive Complex 2 (PRC2), which is essential for embryonic development, binds numerous lncRNAs [23–25], fueling the idea that lncRNAs might be involved in targeting PRC2 to specific gene control elements. For instance, the lncRNA Xist (X-inactivation specific transcripts) binds to PRC2 to deposit repressive histone marks H3K27me3 along the X chromosome followed by inactivation of the marked copy, a mechanism required for dosage compensation in (mammalian) females [26, 27]. In addition to acting in epigenetic control through chromatin modification, emerging evidence has uncovered the underlying crosstalk between lncRNAs and DNA methylation. In this short review, we aim to summarize the relevant findings in this field emphasizing on those lncRNAs that have been identified to physically interact with DNMTs to regulate DNA methylation.Fig. 1


Long noncoding RNAs in DNA methylation: new players stepping into the old game.

Zhao Y, Sun H, Wang H - Cell Biosci (2016)

Genomic context and mechanisms of action of lncRNAs. a LncRNAs can be categorized according to their genomic loci relative to protein-coding genes. Intergenic lncRNAs (lincRNAs) are separate transcription units from protein-coding genes. Among them, a class may be transcribed from enhancers (eRNAs). Intronic lncRNAs are generated from the introns of protein-coding genes without overlapping with exons. Antisense lncRNAs are transcribed in opposite direction of protein-coding genes and overlap with the exons. Divergent lncRNAs are normally initiated from the promoter region of protein-coding genes. b LncRNAs exploit distinct mechanisms to elicit their regulatory roles in gene expression. ① lncRNAs can recruit proteins such as chromatin modifiers to target DNA; ② lncRNAs may act as decoy to titrate away DNA binding proteins like transcription factors; ③ lncRNAs can function as scaffold to bring multiple proteins into a complex; ④ to organize higher-order nuclear structure; ⑤ eRNAs can interact with Mediator and/or Cohesin complex to mediate and/or stabilize chromosomal looping between enhancers and cognate promoters. In cytoplasm, ⑥ lncRNAs can influence translation through intervening the loading of polysomes to mRNAs; ⑦ lncRNAs can serve as miRNA sponges to release their inhibitory roles on target mRNAs; ⑧ lncRNAs can regulate mRNA decay pathway, stabilizing or destabilizing mRNAs through RNA/RNA interaction with mRNA
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4940868&req=5

Fig1: Genomic context and mechanisms of action of lncRNAs. a LncRNAs can be categorized according to their genomic loci relative to protein-coding genes. Intergenic lncRNAs (lincRNAs) are separate transcription units from protein-coding genes. Among them, a class may be transcribed from enhancers (eRNAs). Intronic lncRNAs are generated from the introns of protein-coding genes without overlapping with exons. Antisense lncRNAs are transcribed in opposite direction of protein-coding genes and overlap with the exons. Divergent lncRNAs are normally initiated from the promoter region of protein-coding genes. b LncRNAs exploit distinct mechanisms to elicit their regulatory roles in gene expression. ① lncRNAs can recruit proteins such as chromatin modifiers to target DNA; ② lncRNAs may act as decoy to titrate away DNA binding proteins like transcription factors; ③ lncRNAs can function as scaffold to bring multiple proteins into a complex; ④ to organize higher-order nuclear structure; ⑤ eRNAs can interact with Mediator and/or Cohesin complex to mediate and/or stabilize chromosomal looping between enhancers and cognate promoters. In cytoplasm, ⑥ lncRNAs can influence translation through intervening the loading of polysomes to mRNAs; ⑦ lncRNAs can serve as miRNA sponges to release their inhibitory roles on target mRNAs; ⑧ lncRNAs can regulate mRNA decay pathway, stabilizing or destabilizing mRNAs through RNA/RNA interaction with mRNA
Mentions: A major advance in molecular biology over the past two decades has been the discovery and characterization of function for lncRNAs. The extraordinary maturation in sequencing technology, allowing the detection of low abundance transcripts in genome-wide transcriptomes analyses via massive parallel sequencing, has revealed significant levels of transcriptional activity within the unannotated and annotated regions of genome. Among many of the newly discovered non-coding transcripts, lncRNAs are the transcripts with a length over 200 nt, normally poorly conserved and do not serve as the templates for protein synthesis [16–19]. According to their genomic loci relative to protein-coding counterparts, lncRNAs can be further categorized as long intergenic ncRNAs (lincRNAs), antisense lncRNAs and intronic lncRNAs (Fig. 1) [16, 17]. Many of them are capped, spliced and polyadenylated similar to mRNAs. Recently, another class of lncRNAs, termed enhancer RNAs (eRNAs) generated from regulatory regions of genome, is emerging as important players in transcriptional activation of target mRNAs [20–22]. However, they are normally not spliced or polyadenylated. LncRNAs have been implicated in playing essential roles in every aspect of cellular processes and regulate gene expressions at different levels including chromatin organization, transcriptional control and post-transcriptional regulation (Fig. 1) [17]. The function of lncRNAs cannot currently be predicted from sequence information alone. An emerging theme, however, is the capacity of lncRNAs to modulate gene expression, with many of them participating in epigenetic control through interacting with various types of proteins involved in histone modification or chromatin remodeling. In particular, the Polycomb Repressive Complex 2 (PRC2), which is essential for embryonic development, binds numerous lncRNAs [23–25], fueling the idea that lncRNAs might be involved in targeting PRC2 to specific gene control elements. For instance, the lncRNA Xist (X-inactivation specific transcripts) binds to PRC2 to deposit repressive histone marks H3K27me3 along the X chromosome followed by inactivation of the marked copy, a mechanism required for dosage compensation in (mammalian) females [26, 27]. In addition to acting in epigenetic control through chromatin modification, emerging evidence has uncovered the underlying crosstalk between lncRNAs and DNA methylation. In this short review, we aim to summarize the relevant findings in this field emphasizing on those lncRNAs that have been identified to physically interact with DNMTs to regulate DNA methylation.Fig. 1

Bottom Line: Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level.Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation.Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).

View Article: PubMed Central - PubMed

Affiliation: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

ABSTRACT
Long non-coding RNAs (lncRNAs) are being discovered as a novel family of regulators of gene expression at the epigenetic level. Emerging lines of evidence demonstrate that interplays between lncRNAs and DNA methylation machinery are an important layer of epigenetic regulation. Here in this mini-review we summarize the current findings in the field and focus particularly on the interactions mediated through direct physical association between lncRNAs and DNA methyltransferases (DNMTs).

No MeSH data available.


Related in: MedlinePlus