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PintlincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2

Authors: Marín-Béjar, Oskar; Marchese, Francesco P; Athie, Alejandro; Sánchez, Yolanda; González, Jovanna; Segura, Victor; Huang, Lulu; +7 Authors

PintlincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2

Abstract

Abstract Background The p53 transcription factor is located at the core of a complex wiring of signaling pathways that are critical for the preservation of cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding RNAs (lincRNAs). However, relatively little is known about the role that lincRNAs play in this pathway. Results Here we characterize a lincRNA named Pint (p53 induced noncoding transcript). We show that Pint is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, Pint promotes cell proliferation and survival by regulating the expression of genes of the TGF-β, MAPK and p53 pathways. Pint is a nuclear lincRNA that directly interacts with the Polycomb repressive complex 2 (PRC2), and is required for PRC2 targeting of specific genes for H3K27 tri-methylation and repression. Furthermore, Pint functional activity is highly dependent on PRC2 expression. We have also identified Pint human ortholog (PINT), which presents suggestive analogies with the murine lincRNA. PINT is similarly regulated by p53, and its expression significantly correlates with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, PINT is downregulated in colon primary tumors, while its overexpression inhibits the proliferation of tumor cells, suggesting a possible role as tumor suppressor. Conclusions Our results reveal a p53 autoregulatory negative mechanism where a lincRNA connects p53 activation with epigenetic silencing by PRC2. Additionally, we show analogies and differences between the murine and human orthologs, identifying a novel tumor suppressor candidate lincRNA.

Keywords

p53, 570, Cell Survival, non-coding RNA, Epigenesis, Genetic, Histones, Mice, Transcripció genètica, Transforming Growth Factor beta, Regulació genètica, Animals, Humans, RNA, Small Interfering, Cell Proliferation, Genetic regulation, Genetic transcription, Research, Polycomb Repressive Complex 2, Polycomb repressive complex 2, lincRNA, Colonic Neoplasms, NIH 3T3 Cells, RNA, RNA, Long Noncoding, Mitogen-Activated Protein Kinases, Tumor Suppressor Protein p53, gene regulation

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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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