A large intergenic non-coding RNA induced by p53 mediates global gene repression in the p53 response

By Maite Huarte, M. Guttman, D. Feldser, Manuel Garber, Magdalena J. Koziol, Daniela Kenzelmann-Broz, A. Khalil, Or Zuk, Ido Amit, M. Rabani and 5 more. Cell, 2010

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Summary Recently, more than a thousand large intergenic non-coding 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 mediated apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulating their localization to sets of previously active genes.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f1bfbfea4eb2e8e4b73ebe6dc1775e28c74cf727

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Citations in the corpus

Long Non-Coding RNA in the Pathogenesis of Cancers (2019, background): “lincRNA-p21 can interact with hnRNP-K to be involved in the apoptosis regulated by p53 [260].”
NeST, a long noncoding RNA, controls microbial susceptibility and epigenetic activation of the Ifng locus (2013, neutral): “S.NeST SJL/J mice were fractionated by differential centrifugation (Huarte et al., 2010).”
No-nonsense functions for long noncoding RNAs. (2011, background): “…Targets Unlike the cis-acting lncRNAs described above, a recent screen for lincRNAs (long intergenic noncoding RNAs) regulated by the tumor suppressor transcription factor p53has revealeda lincRNA that targets silencing activity to multiple genes located throughout the genome (Huarte et al., 2010).”
Non-coding RNAs as regulators of embryogenesis (2011, background): “Although the basis of HOTAIR recruitment is unknown and analysis of its role during embryogenesis awaits the generation of mutant alleles, HOTAIR illustrates the potentially wide-ranging effects of lncRNAs as trans -acting regulator”
Regulation of glycolysis by the hypoxia‐inducible factor (HIF): implications for cellular physiology (2020, background): “LincRNA-p21, a key repressor of p53-dependent non-transcriptional responses (Huarte et al. 2010), is strongly induced by hypoxia in a dose- and time-dependent manner through the binding of HIF-1α to C© 2020 The Authors.”
Molecular mechanisms of long noncoding RNAs (2011, background): “LincRNA-p21 is able to exert its effects on chromatin structure and gene expression across multiple sites in the genome (Huarte et al., 2010).”
A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? (2011, background): “…epigenetic mechanisms, including X-inactive specific transcript (XIST), which is implicated in X chromosome inactivation (Brown et al., 1992), and the recently identified large intergenic noncoding (linc)-RNAs (Gong and Maquat, 2011; Guttman et al., 2009; Huarte et al., 2010; Khalil et al., 2009).”
Non-coding RNAs in human disease (2011, background): “Key roles for lincRNAs in certain biological processes are starting to emerge: for example, in the p53-mediated transcriptional response to DNA damag”
Long Non-coding RNAs in the Cytoplasm (2016, background): “0 kb in length, and the encoding gene is located 15 kb upstream of p21/cdkn1a gene [23].”