A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1809 Scopus citations


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. PaperFlick:

Original languageAmerican English
Pages (from-to)409-419
Number of pages11
Issue number3
StatePublished - Aug 2010
Externally publishedYes

Bibliographical note

Funding Information:
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.


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