Beyond the RNA-dependent function of LncRNA genes

  1. Tamer Ali  Is a corresponding author
  2. Phillip Grote  Is a corresponding author
  1. Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University, Germany
  2. Faculty of Science, Benha University, Egypt
4 figures and 1 table


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.

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.

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).

Alteration of genome interactions by lncRNA activity.

DNA:DNA contacts can change upon transcriptional activity of nearby, cis located lncRNA genes.


Table 1
Selection of lncRNA genes with RNA independent function.
LncRNARelative location of respective TSSs target geneLiteratureMode of action
Regulatory element located within the transcription unit
Haunt (Halr1)40 kb downstream of HOXAYin et al., 2015Activation of HOXA
Lockd4 kb downstream of Cdkn1bParalkar et al., 2016Positive regulation of Cdkn1b via loop formation
Meteor80 kb upstream of EomesAlexanian et al., 2017Positive licensing of Eomes expression
ThymoD844 kb downstream of Bcl11bIsoda et al., 2017DNA methylation, CTCF-binding
Pcdhα-asPcdhαCanzio et al., 2019DNA methylation, CTCF-binding
GAL10-ncRNAGAL10 antisense transcriptHouseley et al., 2008GAL10 promoter acetylation
AIRN28 kb Antisense to Igfr2Latos et al., 2012Promoter methylation
Upperhand (Hand2os1)0,1 kb upstream of Hand2Anderson et al., 2016; Han et al., 2019Promotes enhancer accessibility for Hand2 activation
Activity exerted by transcription initiation or elongation
Ftx140 kb upstream of XistFurlan et al., 2018Xist activation independent of Ftx RNA
Chaserr16 kb upstream of Chd2Rom et al., 2019Negative regulation of Chd2
PVT152 kb downstream of MycCho et al., 2018Enhancer boundary element
Handsdown (Handlr)11 kb downstream of Hand2George et al., 2019; Ritter et al., 2019Transcriptional elongation-based enhancer shielding

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  1. Tamer Ali
  2. Phillip Grote
Beyond the RNA-dependent function of LncRNA genes
eLife 9:e60583.