Long noncoding RNAs in the p53 network

The tumor-suppressor protein p53 is activated in response to numerous cellular stresses including DNA damage. p53 functions primarily as a sequence-specific transcription factor that controls the expression of hundreds of protein-coding genes and noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). While the role of protein-coding genes and miRNAs in mediating the effects of p53 has been extensively studied, the physiological function and molecular mechanisms by which p53-regulated lncRNAs act is beginning to be understood. In this review, the authors discuss recent studies on lncRNAs that are directly or indirectly regulated by p53 and how they contribute to the biological outcomes of p53 activation.

LncRNAs in the p53 network

DNA damage activates p53 and its downstream transcriptional targets including lncRNAs. The human and mouse orthologs of lncRNA PINT have contrasting functions. Human PINT has a tumor-suppressor function, whereas mouse ortholog increases cell survival and proliferation. PR-lncRNA1 and PR-LncRNA10 have proapoptotic function and they inhibit cell survival and proliferation. The LncRNA TUG1 has diverse role in different cancer types. TUG1 can promote or inhibit cell proliferation and cell cycle progression depending on the tumor type. The LncRNA NORAD is not a direct transcriptional target of p53 and it interacts with PUMILIO proteins to maintain genomic stability.