The fast-growing RNA-seq technique has found that distinct sets of lncRNAs are expressed in correlation with different physiological and pathological cellular processes . The earliest attempts to elucidate the function of thousands of lncRNAs with highly conserved chromatin signatures in specific biological pathways have shown that 39 lncRNAs were significantly induced in p53-mediated DNA damage response . Most recently, Howard Chang and colleagues performed a screen for transcribed regions around the promoters of cell cycle genes and discovered a new regulatory lncRNA – DINO (damage-induced non-coding RNA), expanding the p53 network (Figure 1A) [41, 47]. DINO is transcribed divergently from CDKN1A (p21) promoter, with ~100-fold increase upon doxorubicin treatment in a p53-dependent manner . In terms of the functions of DINO in the p53-mediated DNA damage pathway, the authors have found that DINO can physically interact with the C-terminal RNA-binding region of p53 and colocalize at multiple p53 target genes including CDKN1A throughout the genome to co-regulate the p53-dependent gene expression and cell cycle arrest in response to DNA damage. More importantly, the microhomology region of DINO interacting with p53 is highly conserved in mammal species, although DINO exhibits poor overall sequence identity across species, suggesting that DINO represent a conserved transcriptional response after DNA damage . To further discern whether the effects observed are due to disruption of the DINO transcripts or the DNA binding platform for other regulatory factors, the study presented two different transgenic knockout mouse models in which the promoter of Dino is either intact or inactivated. Both lines of Dino knockout mice exhibit impaired response to doxorubicin, suggesting that in mouse Dino acts in trans similarly to human DINO . This study identified a new lncRNA that constitutes a feed-forward feedback loop in the p53-dependent DNA damage response. However, it remains unclear how DINO stabilizes p53 and whether DINO mutations are putatively correlated with cancer diagnosis and prognosis.