Pint lincRNA connects the p53 pathway with  epigenetic silencing by the Polycomb repressive  complex 2.
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 aubiquitously 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-b, 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.
Oskar
O
Marín-Béjar
Francesco P
FP
Marchese
Alejandro
A
Athie
Yolanda
Y
Sánchez
Jovanna
J
González
Victor
V
Segura
Lulu
L
Huang
Isabel
I
Moreno
Alfons
A
Navarro
Mariano
M
Monzó
Jesús
J
García-Foncillas
John L
JL
Rinn
Shuling
S
Guo
Maite
M
Huarte
D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D006657:Histones; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D063151:Polycomb Repressive Complex 2; D020928:Mitogen-Activated Protein Kinases