Implication of repeat insertion domains in the trans-activity of the long non-coding RNA ANRIL

Long non-coding RNAs have emerged as critical regulators of cell homeostasis by modulating gene expression at chromatin level for instance. Here, researchers from IMoPA, France 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, the researchers established a list of 65 and 123 genes potentially directly activated and silenced by ANRIL in trans, respectively. They also found that Exon8 of ANRIL, mainly made of transposable elements, contributes to ANRIL genomic association and consequently to its trans-activity. Furthermore, they  showed that Exon8 favors ANRIL’s association with the FIRRE, TPD52L1 and IGFBP3 loci to modulate their expression through H3K27me3 deposition. The researchers also investigated the mechanisms engaged by Exon8 to favor ANRIL’s association with the genome. These data refine ANRIL’s trans-activity and highlight the functional importance of TEs on ANRIL’s activity.

Summary of ANRIL’s functions

ANRIL interacts with 3227 of loci dispersed throughout the HEK293 cell genome sharing a 21-bp motif enriched in G/A residues. Combining ANRIL genomic occupancy with transcriptomic analysis identified 65 and 123 genes potentially trans-activated and silenced by ANRIL in a direct manner, respectively. Exon8 of ANRIL, mainly made of TEs, contributes to ANRIL genomic association and consequently to its trans-activity. ANRIL might also act as splicing regulator.