| Autor: |
Muniz, Lisa, Lazorthes, Sandra, Delmas, Maxime, Ouvrard, Julien, Aguirrebengoa, Marion, Trouche, Didier, Nicolas, Estelle |
| Zdroj: |
RNA Biology; March 2021, Vol. 18 Issue: 3 p404-420, 17p |
| Abstrakt: |
ABSTRACTLong non-coding RNAs (ncRNAs) are major regulators of gene expression and cell fate. The INK4locus encodes the tumour suppressor proteins p15INK4b, p16INK4aand p14ARFrequired for cell cycle arrest and whose expression increases during senescence. ANRILis a ncRNA antisense to the p15gene. In proliferative cells, ANRILprevents senescence by repressing INK4genes through the recruitment of Polycomb-group proteins. In models of replicative and RASval12 oncogene-induced senescence (OIS), the expression of ANRILand Polycomb proteins decreases, thus allowing INK4derepression. Here, we found in a model of RAF1 OIS that ANRILexpression rather increases, due in particular to an increased stability. This led us to search for circular ANRILisoforms, as circular RNAs are rather stable species. We found that the expression of two circular ANRILincreases in several OIS models (RAF1, MEK1 and BRAF). In proliferative cells, they repress p15expression, while in RAF1 OIS, they promote full induction of p15, p16and p14ARFexpression. Further analysis of one of these circular ANRILshows that it interacts with Polycomb proteins and decreases EZH2 Polycomb protein localization and H3K27me3 at the p15and p16promoters, respectively. We propose that changes in the ratio between Polycomb proteins and circular ANRILisoforms allow these isoforms to switch from repressors of p15gene to activators of all INK4genes in RAF1 OIS. Our data reveal that regulation of ANRILexpression depends on the senescence inducer and underline the importance of circular ANRILin the regulation of INK4gene expression and senescence. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
