Cell - A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response
Cell, Volume 142, Issue 3, 409-419, 29 July 2010
Copyright © 2010 Elsevier Inc. All rights reserved.
10.1016/j.cell.2010.06.040

Referred to by: Noncoding RNAs: The Missing “Linc” in p5...

Authors
Maite Huarte, Mitchell Guttman, David Feldser, Manuel Garber, Magdalena J. Koziol, Daniela Kenzelmann-Broz, Ahmad M. Khalil, Or Zuk, Ido Amit, Michal Rabani, Laura D. Attardi, Aviv Regev, Eric S. Lander, Tyler Jacks, John L. RinnSee AffiliationsHint: Rollover Authors and Affiliations The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA The Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA Department of and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA Corresponding author

Highlights
•Several lincRNAs are regulated by p53
•LincRNA-p21 is a bona fide p53 transcriptional target
•LincRNA-p21 mediates global gene repression and apoptosis in the p53 pathway
•LincRNA-p21 represses gene targets through physical association with hnRNP-K

Summary
Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

10.1016/j.cell.2010.06.040
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Cell - A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response