title: G-Quadruplex DNA- and RNA-Specific-Binding Proteins Engineered from the RGG Domain of TLS/FUS.
abstract: Human telomere DNA (Htelo) and telomeric repeat-containing RNA (TERRA) are integral telomere components containing the short DNA repeats d(TTAGGG) and RNA repeats r(UUAGGG), respectively. Htelo and TERRA form G-quadruplexes, but the biological significance of their G-quadruplex formation in telomeres is unknown. Compounds that selectively bind G-quadruplex DNA and RNA are useful for understanding the functions of each G-quadruplex. Here we report that engineered Arg-Gly-Gly repeat (RGG) domains of translocated in liposarcoma containing only Phe (RGGF) and Tyr (RGGY) specifically bind and stabilize the G-quadruplexes of Htelo and TERRA, respectively. Moreover, RGGF inhibits trimethylation of both histone H4 at lysine 20 and histone H3 at lysine 9 at telomeres, while RGGY inhibits only H3 trimethylation in living cells. These findings indicate that G-quadruplexes of Htelo and TERRA have distinct functions in telomere histone methylation.
authors.affiliation: Department of Chemistry, Graduate School of Science, Shizuoka University , 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahama
authors.affiliation: Department of Chemistry, Graduate School of Science, Shizuoka University , 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Miyawaki
authors.affiliation: Department of Chemistry, Graduate School of Science, Shizuoka University , 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Shitara
authors.affiliation: Graduate School of Science and Technology, Hirosaki University , 3 Bunkyo-cho, Hirosaki, Aomori 036-8561, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Mitsuya
authors.affiliation: Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University , 1314-1 Shido, Sanuki-shi, Kagawa 769-2193, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Morikawa
authors.affiliation: Graduate School of Science and Technology, Hirosaki University , 3 Bunkyo-cho, Hirosaki, Aomori 036-8561, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hagihara
authors.affiliation: Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University , 1314-1 Shido, Sanuki-shi, Kagawa 769-2193, Japan.
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Kino
authors.affiliation: Department of Chemistry, Graduate School of Science, Shizuoka University , 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Department of Chemistry, Graduate School of Science, Shizuoka University , 836 Ohya, Suruga, Shizuoka 422-8529, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Oyoshi
mesh_terms: D001120:Arginine / Q000737:chemistry / Q000235:genetics; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D054856:G-Quadruplexes; D005998:Glycine / Q000737:chemistry / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D015202:Protein Engineering; D017434:Protein Structure, Tertiary / Q000235:genetics; D012313:RNA / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000138:chemical synthesis* / Q000737:chemistry; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA; D004247:DNA; D001120:Arginine; D005998:Glycine