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

Huarte, Maite and Guttman, Mitchell and Feldser, David and Garber, Manuel and Koziol, Magdalena J. and Kenzelmann-Broz, Daniela and Khalil, Ahmad M. and Zuk, Or and Amit, Ido and Rabani, Michal and Attardi, Laura D. and Regev, Aviv and Lander, Eric S. and Jacks, Tyler and Rinn, John L. (2010) A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response. Cell, 142 (3). pp. 409-419. ISSN 0092-8674. PMCID PMC2956184. https://resolver.caltech.edu/CaltechAUTHORS:20161121-130357891

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.cell.2010.06.040DOIArticle
http://www.sciencedirect.com/science/article/pii/S0092867410007300PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956184/PubMed CentralArticle
ORCID:
AuthorORCID
Guttman, Mitchell0000-0003-4748-9352
Additional Information:© 2010 Elsevier Inc. Received 6 October 2009, Revised 6 April 2010, Accepted 3 June 2010, Available online 5 August 2010. Published online: July 29, 2010. We would like to thank Loyal A. Goff (Massachusetts Institute of Technology [MIT]) for bioinformatic support, Nadya Dimitrova (MIT) for input on the manuscript, David Garcia (MIT) for experimental assistance, and Sigrid Hart (Broad Institute) for illustration support. J.L.R. is a Damon Runyon-Rachleff, Searle, and Smith Family Foundation Scholar. J.L.R. and A.R. are Richard Merkin Foundation Scholars. This work was supported by the National Institutes of Health (NIH) Director's New Innovator Award, Smith Family Foundation, Damon Runyon Cancer Foundation, Searle Scholar Program, and NIH 1R01CA119176-01.
Funders:
Funding AgencyGrant Number
Richard Merkin Foundation for Stem Cell ResearchUNSPECIFIED
Smith Family FoundationUNSPECIFIED
Damon Runyon Cancer FoundationUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
NIH1R01CA119176-01
Subject Keywords:RNA; CELLCYCLE
Issue or Number:3
PubMed Central ID:PMC2956184
Record Number:CaltechAUTHORS:20161121-130357891
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20161121-130357891
Official Citation: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. Rinn, A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response, Cell, Volume 142, Issue 3, 6 August 2010, Pages 409-419, ISSN 0092-8674, http://dx.doi.org/10.1016/j.cell.2010.06.040. (http://www.sciencedirect.com/science/article/pii/S0092867410007300)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:72205
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:21 Nov 2016 23:24
Last Modified:03 Oct 2019 16:15

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