A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response
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 li...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96038 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826200490398973952 |
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| author | Huarte, Maite Guttman, Mitchell Feldser, David M. Garber, Manuel Koziol, Magdalena J. Kenzelmann-Broz, Daniela Khalil, Ahmad M. Zuk, Or Amit, Ido Rabani, Michal Attardi, Laura D. Regev, Aviv Rinn, John L. Lander, Eric Steven Jacks, Tyler E |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Huarte, Maite Guttman, Mitchell Feldser, David M. Garber, Manuel Koziol, Magdalena J. Kenzelmann-Broz, Daniela Khalil, Ahmad M. Zuk, Or Amit, Ido Rabani, Michal Attardi, Laura D. Regev, Aviv Rinn, John L. Lander, Eric Steven Jacks, Tyler E |
| author_sort | Huarte, Maite |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:37:16Z |
| format | Article |
| id | mit-1721.1/96038 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:37:16Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/960382022-09-27T20:46:59Z A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response Huarte, Maite Guttman, Mitchell Feldser, David M. Garber, Manuel Koziol, Magdalena J. Kenzelmann-Broz, Daniela Khalil, Ahmad M. Zuk, Or Amit, Ido Rabani, Michal Attardi, Laura D. Regev, Aviv Rinn, John L. Lander, Eric Steven Jacks, Tyler E Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Jacks, Tyler E. Guttman, Mitchell Feldser, David M. Regev, Aviv Lander, Eric S. 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. National Institutes of Health (U.S.) (New Innovator Award) Smith Family Foundation Damon Runyon Cancer Research Foundation Searle Scholars Program National Institutes of Health (U.S.) (1R01CA119176-01) 2015-03-17T15:03:32Z 2015-03-17T15:03:32Z 2010-08 2010-04 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/96038 Huarte, Maite, Mitchell Guttman, David Feldser, Manuel Garber, Magdalena J. Koziol, Daniela Kenzelmann-Broz, Ahmad M. Khalil, et al. “A Large Intergenic Noncoding RNA Induced by P53 Mediates Global Gene Repression in the P53 Response.” Cell 142, no. 3 (August 2010): 409–419. © 2010 Elsevier Inc. https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1016/j.cell.2010.06.040 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Huarte, Maite Guttman, Mitchell Feldser, David M. Garber, Manuel Koziol, Magdalena J. Kenzelmann-Broz, Daniela Khalil, Ahmad M. Zuk, Or Amit, Ido Rabani, Michal Attardi, Laura D. Regev, Aviv Rinn, John L. Lander, Eric Steven Jacks, Tyler E A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response |
| title | A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response |
| title_full | A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response |
| title_fullStr | A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response |
| title_full_unstemmed | A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response |
| title_short | A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response |
| title_sort | large intergenic noncoding rna induced by p53 mediates global gene repression in the p53 response |
| url | http://hdl.handle.net/1721.1/96038 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-8567-2049 |
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