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

• DOI: 10.1038/cr.2012.164
• Publication Date: 2012-12-04T11:42:13Z
• Authors: Ali Zhang; Nanjiang Zhou; Jianguo Huang; Qian Liu; Koji Fukuda; Ding Ma; Zhaohui Lu; Cunxue Bai; Kounosuke Watabe; Yin-Yuan Mo
• Keywords: 0301 basic medicine; Chromatin Immunoprecipitation; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; Cell Cycle; HCT116 Cells; Receptor Tyrosine Kinase-like Orphan Receptors; Mass Spectrometry; 03 medical and health sciences; Microscopy, Fluorescence; Cell Line, Tumor; In Situ Nick-End Labeling; Humans; Original Article; RNA, Long Noncoding; Tumor Suppressor Protein p53; DNA Damage

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.