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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.

A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus