Implication of repeat insertion domains in the trans-activity of the long non-coding RNA ANRIL.
Fiche publication
Date publication
avril 2021
Journal
Nucleic acids research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BEHM-ANSMANT Isabelle, Dr BRANLANT Christiane, Pr MOTORINE Iouri, Dr MARCHAND Virginie
Tous les auteurs :
Alfeghaly C, Sanchez A, Rouget R, Thuillier Q, Igel-Bourguignon V, Marchand V, Branlant C, Motorin Y, Behm-Ansmant I, Maenner S
Lien Pubmed
Résumé
Long non-coding RNAs have emerged as critical regulators of cell homeostasis by modulating gene expression at chromatin level for instance. Here, we report that the lncRNA ANRIL, associated with several pathologies, binds to thousands of loci dispersed throughout the mammalian genome sharing a 21-bp motif enriched in G/A residues. By combining ANRIL genomic occupancy with transcriptomic analysis, we established a list of 65 and 123 genes potentially directly activated and silenced by ANRIL in trans, respectively. We also found that Exon8 of ANRIL, mainly made of transposable elements, contributes to ANRIL genomic association and consequently to its trans-activity. Furthermore, we showed that Exon8 favors ANRIL's association with the FIRRE, TPD52L1 and IGFBP3 loci to modulate their expression through H3K27me3 deposition. We also investigated the mechanisms engaged by Exon8 to favor ANRIL's association with the genome. Our data refine ANRIL's trans-activity and highlight the functional importance of TEs on ANRIL's activity.
Référence
Nucleic Acids Res. 2021 Apr 19;: