A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response
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.
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.Attached Files
Accepted Version - nihms227441.pdf
Supplemental Material - mmc1.xls
Supplemental Material - mmc2.xls
Supplemental Material - mmc3.xls
Supplemental Material - mmc4.xls
Supplemental Material - mmc5.pdf
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Additional details
- PMCID
- PMC2956184
- Eprint ID
- 72205
- Resolver ID
- CaltechAUTHORS:20161121-130357891
- Richard Merkin Foundation for Stem Cell Research
- Smith Family Foundation
- Damon Runyon Cancer Foundation
- Searle Scholars Program
- 1R01CA119176-01
- NIH
- Created
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2016-11-21Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field