title: A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus.
abstract: Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially expressed RNAs are mostly repressed during senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class are mainly activated. We show that VAD, a novel antisense vlincRNA strongly induced during senescence, is required for the maintenance of senescence features. VAD modulates chromatin structure in cis and activates gene expression in trans at the INK4 locus, which encodes cell cycle inhibitors important for senescence-associated cell proliferation arrest. Importantly, VAD inhibits the incorporation of the repressive histone variant H2A.Z at INK4 gene promoters in senescent cells. Our data underline the importance of vlincRNAs as sensors of cellular environment changes and as mediators of the correct transcriptional response.
authors.affiliation: 1] Université de Toulouse; UPS; LBCMCP; F-31062 Toulouse, France [2] CNRS; LBCMCP; F-31062 Toulouse, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lazorthes
authors.affiliation: UMR 7216, Université Paris Diderot, 75205 Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Vallot
authors.affiliation: 1] Université de Toulouse; UPS; LBCMCP; F-31062 Toulouse, France [2] CNRS; LBCMCP; F-31062 Toulouse, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briois
authors.affiliation: 1] Université de Toulouse; UPS; LBCMCP; F-31062 Toulouse, France [2] CNRS; LBCMCP; F-31062 Toulouse, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Aguirrebengoa
authors.affiliation: CEA, iBiTec-S, SBIGeM/CNRS-FRE3377 and I2BC/Université Paris-Sud and Paris-Saclay, 91191 Gif-sur-Yvette, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Thuret
authors.affiliation: St Laurent Institute, Woburn, Massachusetts 01801, USA.
authors.forename: Georges
authors.initials: G
authors.lastname: St Laurent
authors.affiliation: UMR 7216, Université Paris Diderot, 75205 Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Rougeulle
authors.affiliation: 1] St Laurent Institute, Woburn, Massachusetts 01801, USA [2] Institute of Genomics, Huaqiao University School of Medicine, Xiamen 361021, China [3] Academy of Biology and Biotechnology, South Federal University, Rostov-on-Don, Russia.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kapranov
authors.affiliation: CEA, iBiTec-S, SBIGeM/CNRS-FRE3377 and I2BC/Université Paris-Sud and Paris-Saclay, 91191 Gif-sur-Yvette, France.
authors.forename: Carl
authors.initials: C
authors.lastname: Mann
authors.affiliation: 1] Université de Toulouse; UPS; LBCMCP; F-31062 Toulouse, France [2] CNRS; LBCMCP; F-31062 Toulouse, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Trouche
authors.affiliation: 1] Université de Toulouse; UPS; LBCMCP; F-31062 Toulouse, France [2] CNRS; LBCMCP; F-31062 Toulouse, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Nicolas
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D002843:Chromatin / Q000235:genetics; D006570:Heterochromatin / Q000235:genetics; D006801:Humans; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: D002843:Chromatin; D006570:Heterochromatin; D022661:RNA, Untranslated