A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins.
Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cell physiology, but many of which have no known function. CDKN1A/p21 is an important inhibitor of the cell-cycle, regulator of the DNA damage response and effector of the tumor suppressor p53, playing a crucial role in tumor develop...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3991591?pdf=render |
| _version_ | 1818987060600504320 |
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| author | Masamitsu Negishi Somsakul P Wongpalee Sukumar Sarkar Jonghoon Park Kyung Yong Lee Yoshiyuki Shibata Brian J Reon Roger Abounader Yutaka Suzuki Sumio Sugano Anindya Dutta |
| author_facet | Masamitsu Negishi Somsakul P Wongpalee Sukumar Sarkar Jonghoon Park Kyung Yong Lee Yoshiyuki Shibata Brian J Reon Roger Abounader Yutaka Suzuki Sumio Sugano Anindya Dutta |
| author_sort | Masamitsu Negishi |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cell physiology, but many of which have no known function. CDKN1A/p21 is an important inhibitor of the cell-cycle, regulator of the DNA damage response and effector of the tumor suppressor p53, playing a crucial role in tumor development and prevention. In order to identify a regulator for tumor progression, we performed an siRNA screen of human lncRNAs required for cell proliferation, and identified a novel lncRNA, APTR, that acts in trans to repress the CDKN1A/p21 promoter independent of p53 to promote cell proliferation. APTR associates with the promoter of CDKN1A/p21 and this association requires a complementary-Alu sequence encoded in APTR. A different module of APTR associates with and recruits the Polycomb repressive complex 2 (PRC2) to epigenetically repress the p21 promoter. A decrease in APTR is necessary for the induction of p21 after heat stress and DNA damage by doxorubicin, and the levels of APTR and p21 are anti-correlated in human glioblastomas. Our data identify a new regulator of the cell-cycle inhibitor CDKN1A/p21 that acts as a proliferative factor in cancer cell lines and in glioblastomas and demonstrate that Alu elements present in lncRNAs can contribute to targeting regulatory lncRNAs to promoters. |
| first_indexed | 2024-12-20T19:00:41Z |
| format | Article |
| id | doaj.art-dbe43e105b9249f599e1f75789e33cc3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T19:00:41Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-dbe43e105b9249f599e1f75789e33cc32022-12-21T19:29:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9521610.1371/journal.pone.0095216A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins.Masamitsu NegishiSomsakul P WongpaleeSukumar SarkarJonghoon ParkKyung Yong LeeYoshiyuki ShibataBrian J ReonRoger AbounaderYutaka SuzukiSumio SuganoAnindya DuttaLong noncoding RNAs (lncRNAs) have emerged as a major regulator of cell physiology, but many of which have no known function. CDKN1A/p21 is an important inhibitor of the cell-cycle, regulator of the DNA damage response and effector of the tumor suppressor p53, playing a crucial role in tumor development and prevention. In order to identify a regulator for tumor progression, we performed an siRNA screen of human lncRNAs required for cell proliferation, and identified a novel lncRNA, APTR, that acts in trans to repress the CDKN1A/p21 promoter independent of p53 to promote cell proliferation. APTR associates with the promoter of CDKN1A/p21 and this association requires a complementary-Alu sequence encoded in APTR. A different module of APTR associates with and recruits the Polycomb repressive complex 2 (PRC2) to epigenetically repress the p21 promoter. A decrease in APTR is necessary for the induction of p21 after heat stress and DNA damage by doxorubicin, and the levels of APTR and p21 are anti-correlated in human glioblastomas. Our data identify a new regulator of the cell-cycle inhibitor CDKN1A/p21 that acts as a proliferative factor in cancer cell lines and in glioblastomas and demonstrate that Alu elements present in lncRNAs can contribute to targeting regulatory lncRNAs to promoters.http://europepmc.org/articles/PMC3991591?pdf=render |
| spellingShingle | Masamitsu Negishi Somsakul P Wongpalee Sukumar Sarkar Jonghoon Park Kyung Yong Lee Yoshiyuki Shibata Brian J Reon Roger Abounader Yutaka Suzuki Sumio Sugano Anindya Dutta A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. PLoS ONE |
| title | A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. |
| title_full | A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. |
| title_fullStr | A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. |
| title_full_unstemmed | A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. |
| title_short | A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. |
| title_sort | new lncrna aptr associates with and represses the cdkn1a p21 promoter by recruiting polycomb proteins |
| url | http://europepmc.org/articles/PMC3991591?pdf=render |
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