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Review
. 2020 Oct 23:9:e60583.
doi: 10.7554/eLife.60583.

Beyond the RNA-dependent function of LncRNA genes

Affiliations
Review

Beyond the RNA-dependent function of LncRNA genes

Tamer Ali et al. Elife. .

Abstract

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.

Keywords: 3D genome; gene regulation; genetics; genomics; lncRNA.

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Conflict of interest statement

TA, PG No competing interests declared

Figures

Figure 1.
Figure 1.. LncRNA genes in the genome.
(A) Overview of genes and transcript numbers in the human genome (GENCODE v35). Circle area represents relative quantities. (B) Schematics of three possible functional properties of lncRNA loci.
Figure 2.
Figure 2.. Distinguishing features of transcript generation of PCGs and lncRNAs (A) LncRNA and (B) mRNAs: lncRNA genes are lowly expressed as fewer transcription factors (TFs) bind the promoter.
In addition, lncRNA TSS, exon and/or pA site more often associate with transposable elements (TEs), while TEs contribute mostly to UTRs and/or introns of mRNAs. In addition, mRNAs are more efficiently spliced.
Figure 3.
Figure 3.. Modulation of gene expression by lncRNA transcription.
(A) Transcriptional activity modulates DNA methylation and thereby alters occupation of DNA binding factors within the gene body, for example CTCF. The POL2 complex is indicated in violet. Black drumsticks indicate methylated CpGs, white drumstick non-methylated CpGs. (B) LncRNA expression alters promoter (Prom.) activity by modifying e.g. acetylation of histones at TSS sites. (C) Transcription elongation can activate poised enhancers within their gene body (only acetylation shown).
Figure 4.
Figure 4.. Alteration of genome interactions by lncRNA activity.
DNA:DNA contacts can change upon transcriptional activity of nearby, cis located lncRNA genes.

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