DNA G-Quadruplex-Binding Protein Developed Using the RGG Domain of Translocated in Liposarcoma/Fused in Sarcoma Inhibits Transcription of bcl-2

Luthfi Lulul Ulum; Yamato Karikome; Ryota Yagi; Tomoe Kawashima; Akinori Ishihara; Takanori Oyoshi

doi:10.1021/acsomega.3c00050

DNA G-Quadruplex-Binding Protein Developed Using the RGG Domain of Translocated in Liposarcoma/Fused in Sarcoma Inhibits Transcription of bcl-2

ACS Omega. 2023 Mar 9;8(11):10459-10465. doi: 10.1021/acsomega.3c00050. eCollection 2023 Mar 21.

Authors

Luthfi Lulul Ulum¹, Yamato Karikome², Ryota Yagi², Tomoe Kawashima², Akinori Ishihara², Takanori Oyoshi^{1

2

3}

Affiliations

¹ Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
² Graduate School of Integrated Science and Technology, Shizuoka University, 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
³ Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya, Suruga, Shizuoka 422-8529, Japan.

Abstract

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 in vitro. Furthermore, RGGF binds to the DNA G4 of the bcl-2 promoter in vitro. RGGF overexpression in HeLa cells represses bcl-2 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.