Context-Dependent Function of Long Noncoding RNA PURPL i n Transcriptome Regulation during p53 Activation

Hartford Corrine Corrina R.; Shrestha Roshan L.; Pongor LorincZhao YongmeiChen XiongfongFromont CarolineChaudhary RituLi Xiao LingPasterczyk Katherine R.Kumar RaviMuys Bruna R.Tsitsipatis DimitriosChari RajGorospe MyriamAladjem Mirit IKhan JavedBasrai Munira A.Grammatikakis loannisLal Ashish

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Context-Dependent Function of Long Noncoding RNA PURPL i n Transcriptome Regulation during p53 Activation

机译：Context-Dependent Function of Long Noncoding RNA PURPL i n Transcriptome Regulation during p53 Activation

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PURPL is a p53-induced IncRNA 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 similar to 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.

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《Molecular and Cellular Biology》 |2022年第12期|共19页
作者
Hartford Corrine Corrina R.; Shrestha Roshan L.; Pongor LorincZhao YongmeiChen XiongfongFromont CarolineChaudhary RituLi Xiao LingPasterczyk Katherine R.Kumar RaviMuys Bruna R.Tsitsipatis DimitriosChari RajGorospe MyriamAladjem Mirit IKhan JavedBasrai Munira A.Grammatikakis loannisLal Ashish;
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NIA;

NCI;

H Lee Moffitt Canc Ctr & Res Inst;

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正文语种英语
中图分类分子生物学;
关键词
alternative splicing; context-dependent; CRISPRi; intron retention; Iso-Seq; LINC01021; liver cancer; IncRNA; mitosis; p53; PacBio; PURPL; CRISPR/Cas9; cell cycle checkpoints; MESSENGER-RNA; LNCRNA; LOCALIZATION; EXPRESSION; SET; IDENTIFICATION; METASTASIS; PROTEINS; NETWORKS; PROTECTS;

Context-Dependent Function of Long Noncoding RNA PURPL i n Transcriptome Regulation during p53 Activation

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