title: The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage.
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.
authors.affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794-9621, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Zhang
authors.forename: Nanjiang
authors.initials: N
authors.lastname: Zhou
authors.forename: Jianguo
authors.initials: J
authors.lastname: Huang
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Lu
authors.forename: Cunxue
authors.initials: C
authors.lastname: Bai
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Watabe
authors.forename: Yin-Yuan
authors.initials: YY
authors.lastname: Mo
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D062085:RNA, Long Noncoding / Q000235:genetics*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; D057050:Receptor Tyrosine Kinase-like Orphan Receptors