Vučićević Dubravka, Gehre Maja, Dhamija Sonam, Friis-Hansen Lennart, Meierhofer David, Sauer Sascha, Ørom Ulf Andersson
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Oncotarget. 2016 Jun 7;7(23):33934-47. doi: 10.18632/oncotarget.8985.
Long non-coding RNAs are important regulators of gene expression and signaling pathways. The expression of long ncRNAs is dysregulated in cancer and other diseases. The identification and characterization of long ncRNAs is often challenging due to their low expression level and localization to chromatin. Here, we identify a functional long ncRNA, PARROT (Proliferation Associated RNA and Regulator Of Translation) transcribed by RNA polymerase II and expressed at a relatively high level in a number of cell lines. The PARROT long ncRNA is associated with proliferation in both transformed and normal cell lines. We characterize the long ncRNA PARROT as an upstream regulator of c-Myc affecting cellular proliferation and translation using RNA sequencing and mass spectrometry following depletion of the long ncRNA. PARROT is repressed during senescence of human mammary epithelial cells and overexpressed in some cancers, suggesting an important association with proliferation through regulation of c-Myc. With this study, we add to the knowledge of cytoplasmic functional long ncRNAs and extent the long ncRNA-Myc regulatory network in transformed and normal cells.
长链非编码RNA是基因表达和信号通路的重要调节因子。长链非编码RNA的表达在癌症和其他疾病中失调。由于其低表达水平和定位于染色质,长链非编码RNA的鉴定和表征往往具有挑战性。在这里,我们鉴定了一种功能性长链非编码RNA,即PARROT(增殖相关RNA和翻译调节因子),它由RNA聚合酶II转录,并在许多细胞系中以相对较高的水平表达。PARROT长链非编码RNA在转化细胞系和正常细胞系中均与增殖相关。我们通过在长链非编码RNA缺失后进行RNA测序和质谱分析,将长链非编码RNA PARROT表征为c-Myc的上游调节因子,影响细胞增殖和翻译。PARROT在人乳腺上皮细胞衰老过程中受到抑制,在某些癌症中过表达,提示其通过调节c-Myc与增殖存在重要关联。通过这项研究,我们增加了对细胞质功能性长链非编码RNA的认识,并扩展了转化细胞和正常细胞中的长链非编码RNA-Myc调节网络。