title: Regulation of telomere length by G-quadruplex telomere DNA- and TERRA-binding protein TLS/FUS.
abstract: Mammalian telomeres comprise noncoding TTAGGG repeats in double-stranded regions with a single-stranded TTAGGG repeat 3' overhang and are bound by a multiprotein complex with a telomeric repeat-containing RNA (TERRA) containing a UUAGGG repeat as a G-quadruplex noncoding RNA. TLS/FUS is a human telomere-binding protein that was first identified as an oncogenic fusion protein in human myxoid and round-cell liposarcoma. Here, we show that the Arg-Gly-Gly domain in the C-terminal region of TLS forms a ternary complex with human telomere G-quadruplex DNA and TERRA in vitro. Furthermore, TLS binds to G-quadruplex telomere DNA in double-stranded regions and to G-quadruplex TERRA, which regulates histone modifications of telomeres and telomere length in vivo. Our findings suggest that the G-quadruplex functions as a scaffold for the telomere-binding protein, TLS, to regulate telomere length by histone modifications.
authors.affiliation: Faculty of Science, Department of Chemistry, Shizuoka University, 836 Ohya Suruga, Shizuoka 422-8529, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahama
authors.forename: Asami
authors.initials: A
authors.lastname: Takada
authors.forename: Shota
authors.initials: S
authors.lastname: Tada
authors.forename: Mai
authors.initials: M
authors.lastname: Shimizu
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Sayama
authors.forename: Riki
authors.initials: R
authors.lastname: Kurokawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Oyoshi
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D054856:G-Quadruplexes; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000737:chemistry / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000235:genetics*; D059506:Telomere Shortening
chemical_list: D006657:Histones; D034702:RNA-Binding Protein FUS; D012313:RNA; D004247:DNA