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

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).

Synthesis, crystal structure and properties of a quaternary oxide with a new structure type, BiGaTiO.

A new quaternary oxide, BiGaTiO (bismuth gallium tetratitanium undecaoxide), was prepared by heating a mixture of the binary oxides at 1373 K in air. BiGaTiO melts at 1487 K and prismatic single crystals were obtained from a sample melted at 1523 K and solidified by furnace cooling. The structure of BiGaTiO was analyzed using single-crystal X-ray diffraction to be of a new type that crystallized in the space group Cmcm.

G-quadruplex binding ability of TLS/FUS depends on the β-spiral structure of the RGG domain.

The RGG domain, defined as closely spaced Arg-Gly-Gly repeats, is a DNA and RNA-binding domain in various nucleic acid-binding proteins. Translocated in liposarcoma (TLS), which is also called FUS, is a protein with three RGG domains, RGG1, RGG2 and RGG3. TLS/FUS binding to G-quadruplex telomere DNA and telomeric repeat-containing RNA depends especially on RGG3, comprising Arg-Gly-Gly repeats with proline- and arginine-rich regions.

Plastic roles of phenylalanine and tyrosine residues of TLS/FUS in complex formation with the G-quadruplexes of telomeric DNA and TERRA.

The length of a telomere is regulated via elongation and shortening processes. Telomeric DNA and telomeric repeat-containing RNA (TERRA), which both contain G-rich repeated sequences, form G-quadruplex structures. Previously, translocated in liposarcoma (TLS) protein, also known as fused in sarcoma (FUS) protein, was found to form a ternary complex with the G-quadruplex structures of telomeric DNA and TERRA.