The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage  

作　　者：Ali Zhang Nanjiang Zhou Jianguo Huang Qian Liu Koji Fukuda Ding Ma Zhaohui Lu Cunxue Bai Kounosuke Watabe Yin-Yuan Mo 

机构地区：[1]Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794-9621, USA [2]Cancer Biology Research Center, Tongji Hospital Tongli Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China [3]Department of Endocrinology, PLA General Hospital, Beijing 100853, China [4]Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China [5]Cancer Institute, University of Mississippi Medical Center Cancer Institute, 2500 N State St, Guyton 2, Suite G651, Jackson, MS 39216-4505, USA

出　　处：《Cell Research》2013年第3期340-350,共11页细胞研究（英文版）

摘　　要：It is well known that upon stress, the level of the tumor suppressor p53 is remarkably elevated. However, despite extensive studies, the underlying mechanism involving important inter-players for stress-induced p53 regulation is still not fully understood. We present evidence that the human IincRNA-RoR （RoR） is a strong negative regulator of p53. Unlike MDM2 that causes p53 degradation through the ubiquitin-proteasome pathway, RoR suppresses p53 translation through direct interaction with the heterogeneous nuclear ribonucleoprotein I （hnRNP I）. Importantly, a 28-base RoR sequence carrying hnRNP I binding motifs is essential and sufficient for p53 repression. We further show that RoR inhibits p53-mediated cell cycle arrest and apoptosis. Finally, we demonstrate a RoR-p53 autoregula- tory feedback loop where p53 transcriptionally induces RoR expression. Together, these results suggest that the RoR- hnRNP I-p53 axis may constitute an additional surveillance network for the cell to better respond to various stresses.It is well known that upon stress, the level of the tumor suppressor p53 is remarkably elevated. However, despite extensive studies, the underlying mechanism involving important inter-players for stress-induced p53 regulation is still not fully understood. We present evidence that the human IincRNA-RoR （RoR） is a strong negative regulator of p53. Unlike MDM2 that causes p53 degradation through the ubiquitin-proteasome pathway, RoR suppresses p53 translation through direct interaction with the heterogeneous nuclear ribonucleoprotein I （hnRNP I）. Importantly, a 28-base RoR sequence carrying hnRNP I binding motifs is essential and sufficient for p53 repression. We further show that RoR inhibits p53-mediated cell cycle arrest and apoptosis. Finally, we demonstrate a RoR-p53 autoregula- tory feedback loop where p53 transcriptionally induces RoR expression. Together, these results suggest that the RoR- hnRNP I-p53 axis may constitute an additional surveillance network for the cell to better respond to various stresses.

关 键 词：lncRNA P53 hnRNPI 

分 类 号：Q2[生物学—细胞生物学] Q523