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:
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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.