The sequencing of the human genome has revealed that protein-coding genes correspond only to approximately 2% of the genome. Despite of this, the vast majority of the mammalian genome is actively transcribed. Thus, it is intriguing what this non-coding RNA (ncRNA), which was previously considered as transcriptional “noise”, is doing in the cell. New high-throughput technologies and novel RNA methodologies have demonstrated that there are different classes of ncRNA and that they may have pivotal roles in cellular processes. The project proposed here is focused on understanding the role of a recently discovered class of ncRNAs, long non-coding RNAs (lncRNAs). Although this is largely an unexplored field and the majority of lncRNAs remain to be characterized, several lncRNAs have been demonstrated to have important roles in processes such as proliferation or differentiation and hereby inferred roles in diseases including cancer. This highlights the importance of elucidating the roles of lncRNAs in cellular physiology and pathology. In the present project, my aim is identifying lncRNAs deregulated and functionally important in senescence, the process in which cells enter an irreversible growth arrest following oncogenic insults or telomere erosion. Towards this, I will use broad set of cell biology, biochemistry and genetics approaches and I will combine my previous expertise in RNA biology with new knowledge and cutting edge techniques in the ncRNA field that I will acquire in the host group. I will take advantage of collaborations from several European networks as well as from a Marie Curie Initial Training Network that the host PI was recently awarded. This project will help not only to uncover unknown functions of lncRNAs in cellular regulation but also, since oncogene-induced senescence is considered a mechanism to protect the cell against cancer, it holds the potential to discover lncRNAs that can be used as diagnosis markers and therapeutic interventions.