Ulum Luthfi Lulul, Karikome Yamato, Yagi Ryota, Kawashima Tomoe, Ishihara Akinori, Oyoshi Takanori
Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
Graduate School of Integrated Science and Technology, Shizuoka University, 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
ACS Omega. 2023 Mar 9;8(11):10459-10465. doi: 10.1021/acsomega.3c00050. eCollection 2023 Mar 21.
The G-quadruplexes (G4s) in the genome are important drug targets because they regulate gene expression and the genome structure. Several small molecules that bind the G4 have been developed, but few artificial G4 binding proteins have been reported. We previously reported a novel DNA G4 binding protein (RGGF) engineered using the Arg-Gly-Gly repeat (RGG) domain of TLS (translocated in liposarcoma), also known as FUS (fused in sarcoma) protein (TLS/FUS). Here, we show that RGGF recognizes DNA loops in the G4 and preferentially binds DNA G4 with long loops . Furthermore, RGGF binds to the DNA G4 of the promoter . RGGF overexpression in HeLa cells represses transcription. On the basis of these findings, G4 binding protein engineered from the RGG domain will be useful for investigating G4 transcriptional function in the genome.
基因组中的G-四链体（G4s）是重要的药物靶点，因为它们调控基因表达和基因组结构。已经开发出几种与G4结合的小分子，但报道的人工G4结合蛋白却很少。我们之前报道了一种新型DNA G4结合蛋白（RGGF），它是利用TLS（易位性脂肪肉瘤）的精氨酸-甘氨酸-甘氨酸重复序列（RGG）结构域构建的，TLS也被称为FUS（肉瘤融合蛋白）（TLS/FUS）。在此，我们表明RGGF识别G4中的DNA环，并优先结合具有长环的DNA G4。此外，RGGF与启动子的DNA G4结合。在HeLa细胞中过表达RGGF会抑制转录。基于这些发现，由RGG结构域构建的G4结合蛋白将有助于研究基因组中G4的转录功能。
