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- Title
The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage.
- Authors
Zhang, Ali; Zhou, Nanjiang; Huang, Jianguo; Liu, Qian; Fukuda, Koji; Ma, Ding; Lu, Zhaohui; Bai, Cunxue; Watabe, Kounosuke; Mo, Yin-Yuan
- Abstract
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 lincRNA-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 autoregulatory 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.
- Subjects
NON-coding RNA; DNA damage; GENETIC repressors; UBIQUITIN; CELL cycle
- Publication
Cell Research, 2013, Vol 23, Issue 3, p340
- ISSN
1001-0602
- Publication type
Article
- DOI
10.1038/cr.2012.164