PDF(Pubmed)
Abstract：
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes responsible for linking a transfer RNA (tRNA) with its cognate amino acid present in all the kingdoms of life. Besides their aminoacyl-tRNA synthetase activity, it was described that many of these enzymes can carry out non-canonical functions. They were shown to be involved in important biological processes such as metabolism, immunity, development, angiogenesis and tumorigenesis. In the present work, we provide evidence that tryptophanyl-tRNA synthetase might be involved in a negative feedback loop mitigating the expression of certain interferon-γ-induced genes. Mining the available TCGA and Gtex data, we found that WARS was highly expressed in cutaneous melanoma (SKCM) compared to other cancers and is of good prognosis for this particular cancer type. WARS expression correlates with genes involved in antigen processing and presentation but also transcription factors involved in IFN-γ signaling such as STAT1. In addition, WARS was found in complex with STAT1 in A375 cells treated with IFN-γ. Finally, we showed that knocking down WARS expression during IFN-γ stimulation further increases the expression of GBP2, APOL1, ISG15, HLA-A and IDO1.
摘要：
氨酰基-tRNA合成酶（aaRS）是负责将转移RNA（tRNA）与所有生命界中存在的同源氨基酸连接的必需酶。除了它们的氨酰tRNA合成酶活性，据描述，许多这些酶可以执行非规范的功能。它们被证明参与了重要的生物过程，如新陈代谢，豁免权,发展,血管生成和肿瘤发生。在目前的工作中,我们提供的证据表明,色氨酸-tRNA合成酶可能参与减轻某些干扰素-γ诱导基因表达的负反馈回路.挖掘可用的TCGA和Gtex数据，我们发现,与其他癌症相比,WARS在皮肤黑色素瘤(SKCM)中高表达,并且对于该特定癌症类型具有良好的预后.WARS表达与参与抗原加工和呈递的基因以及参与IFN-γ信号传导的转录因子(如STAT1)相关。此外,在用IFN-γ处理的A375细胞中发现WARS与STAT1的复合物。最后,我们发现，在IFN-γ刺激期间敲低WARS的表达进一步增加了GBP2，APOL1，ISG15，HLA-A和IDO1的表达。
