Project description:The goal of our study is to investigate the role of the p53-induced lncRNA PURPL in the context of liver cancer. To achieve this, we identified transcript variants of PURPL expressed in liver cancer cells and assayed for the transcriptome changes caused by PURPL knockdown after p53 induction.
Project description:The goal of our study is to investigate the role of the p53-induced lncRNA PURPL in the context of liver cancer. To achieve this, we identified transcript variants of PURPL expressed in liver cancer cells and assayed for the transcriptome changes caused by PURPL knockdown after p53 induction.
Project description:The goal of our study is to investigate the role of the p53-induced lncRNA PURPL in the context of liver cancer. To achieve this, we identified transcript variants of PURPL expressed in liver cancer cells and assayed for the transcriptome changes caused by PURPL knockdown after p53 induction.
Project description:Analysis of changes in gene expression profile upon depletion of PURPL in HCT116 cells. The hypothesis in this study is that PURPL regulates gene expression in the p53 pathway.
Project description:PURPL is a p53-induced lncRNA that suppresses basal p53 levels. Here, we investigated PURPL 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 PURPL transcripts that have a retained intron and/or previously unannotated exons. To determine PURPL function upon p53 activation, we performed transcriptome sequencing (RNA-Seq) after depleting PURPL using CRISPR interference (CRISPRi), followed by Nutlin treatment to induce p53. Strikingly, although loss of PURPL in untreated cells altered the expression of only 7 genes, loss of PURPL resulted in altered expression of ~800 genes upon p53 activation, revealing a context-dependent function of PURPL. Pathway analysis suggested that PURPL 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 PURPL depletion. Collectively, these data identify novel transcripts from the PURPL locus and suggest that PURPL delicately moderates the expression of mitotic genes in the context of p53 activation to control cell cycle arrest.
Project description:Cellular senescence involves heterochromatin reorganization and aberrant gene expression. We demonstrate that the nuclear-enriched lncRNA PURPL regulates senescence-associated chromatin dynamics by modulating H3K9me3 deposition. PURPL knockdown increased global H3K9me3 levels while its overexpression reduced this repressive mark. Genome-wide analysis revealed 411 loci with PURPL-dependent H3K9me3 changes, including the aging-related gene SERPINE1, where H3K9me3 accumulation correlated with transcriptional repression. These findings establish PURPL as an epigenetic regulator of senescence through targeted control of heterochromatin formation.
Project description:ellular senescence is a fundamental driver of aging and age-related diseases, with long non-coding RNAs (lncRNAs) emerging as critical regulators of this process. Here, we identify PURPL as a bidirectional modulator of senescence in human fibroblasts. Through comparative transcriptomic analysis of replicative and doxorubicin-induced senescence models, we discovered PURPL as the most significantly upregulated lncRNA common to both systems. CRISPR interference (CRISPRi)-mediated PURPL depletion in senescent cells reversed hallmark aging phenotypes, including restoration of LMNB1 expression, suppression of p21, and reduced SA-β-gal activity. Conversely, PURPL overexpression in young fibroblasts recapitulated senescence signatures, inducing extracellular matrix reorganization and cell cycle arrest pathways. RNA-seq revealed PURPL overexpression dysregulated 1,633 genes, mirroring natural aging transcriptomes. These opposing effects establish PURPL as a central regulator of cellular senescence, suggesting its therapeutic potential for age-related conditions. Our findings provide mechanistic insights into lncRNA-mediated senescence control and highlight PURPL as a novel target for aging intervention strategies.