The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage.
The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage.
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作者：
众所周知，在应激状态下，肿瘤抑制因子p53的水平显著升高。然而，尽管进行了广泛的研究，涉及应激诱导的p53调控的重要内部参与者的潜在机制仍未完全了解。我们提出的证据表明，人类linrna -RoR （RoR）是p53的强负调控因子。与MDM2通过泛素-蛋白酶体途径导致p53降解不同，RoR通过与异质核核糖核蛋白I （hnRNP I）的直接相互作用抑制p53的翻译。重要的是，携带hnRNP I结合基序的28碱基RoR序列是p53抑制的必要和充分条件。我们进一步证明RoR抑制p53介导的细胞周期阻滞和凋亡。最后，我们证明了一个由p53转录诱导RoR表达的RoR-p53自调节反馈回路。总之，这些结果表明，RoR-hnRNP I-p53轴可能构成一个额外的监视网络，使细胞更好地响应各种应激。
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.
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Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
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