Circular ANRIL isoforms switch from repressors to activators of p15/CDKN2B expression during RAF1 oncogene-induced senescence
| العنوان: | Circular ANRIL isoforms switch from repressors to activators of p15/CDKN2B expression during RAF1 oncogene-induced senescence |
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| المؤلفون: | Didier Trouche, Lisa Muniz, Maxime Delmas, Sandra Lazorthes, Marion Aguirrebengoa, Estelle Nicolas, Julien Ouvrard |
| المساهمون: | Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | RNA Biology RNA Biology, Taylor & Francis, 2020, pp.1-17. ⟨10.1080/15476286.2020.1812910⟩ |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Regulation of gene expression, Senescence, 0303 health sciences, [SDV]Life Sciences [q-bio], EZH2, Repressor, Cell Biology, Cell fate determination, Biology, Non-coding RNA, Cell biology, 03 medical and health sciences, 0302 clinical medicine, p14arf, 030220 oncology & carcinogenesis, Gene expression, Molecular Biology, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology |
| الوصف: | Long non-coding RNAs (ncRNAs) are major regulators of gene expression and cell fate. The INK4 locus encodes the tumour suppressor proteins p15INK4b, p16INK4a and p14ARF required for cell cycle arrest and whose expression increases during senescence. ANRIL is a ncRNA antisense to the p15 gene. In proliferative cells, ANRIL prevents senescence by repressing INK4 genes through the recruitment of Polycomb-group proteins. In models of replicative and RASval12 oncogene-induced senescence (OIS), the expression of ANRIL and Polycomb proteins decreases, thus allowing INK4 derepression. Here, we found in a model of RAF1 OIS that ANRIL expression rather increases, due in particular to an increased stability. This led us to search for circular ANRIL isoforms, as circular RNAs are rather stable species. We found that the expression of two circular ANRIL increases in several OIS models (RAF1, MEK1 and BRAF). In proliferative cells, they repress p15 expression, while in RAF1 OIS, they promote full induction of p15, p16 and p14ARF expression. Further analysis of one of these circular ANRIL shows that it interacts with Polycomb proteins and decreases EZH2 Polycomb protein localization and H3K27me3 at the p15 and p16 promoters, respectively. We propose that changes in the ratio between Polycomb proteins and circular ANRIL isoforms allow these isoforms to switch from repressors of p15 gene to activators of all INK4 genes in RAF1 OIS. Our data reveal that regulation of ANRIL expression depends on the senescence inducer and underline the importance of circular ANRIL in the regulation of INK4 gene expression and senescence. |
| اللغة: | English |
| تدمد: | 1547-6286 1555-8584 |
| DOI: | 10.1101/2020.04.28.065888 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5532a9fccd5a149926673fa5790698baTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5532a9fccd5a149926673fa5790698ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15476286 15558584 |
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| DOI: | 10.1101/2020.04.28.065888 |