Context-Dependent Function of Long Noncoding RNA in Transcriptome Regulation during p53 Activation.

is a p53-induced lncRNA that suppresses basal p53 levels. Here, we investigated upon p53 activation in liver cancer cells, where it is expressed at significantly higher levels than other cell types. Using isoform sequencing, we discovered novel transcripts that have a retained intron and/or previously unannotated exons. To determine function upon p53 activation, we performed transcriptome sequencing (RNA-Seq) after depleting using CRISPR interference (CRISPRi), followed by Nutlin treatment to induce p53. Strikingly, although loss of in untreated cells altered the expression of only 7 genes, loss of resulted in altered expression of ~800 genes upon p53 activation, revealing a context-dependent function of . Pathway analysis suggested that is important for fine-tuning the expression of specific genes required for mitosis. Consistent with these results, we observed a significant decrease in the percentage of mitotic cells upon depletion. Collectively, these data identify novel transcripts from the locus and suggest that delicately moderates the expression of mitotic genes in the context of p53 activation to control cell cycle arrest.