title: Specific binding of modified RGG domain in TLS/FUS to G-quadruplex RNA: tyrosines in RGG domain recognize 2'-OH of the riboses of loops in G-quadruplex.
abstract: Telomeric repeat-containing RNA (TERRA), which contains tandem arrays of short RNA repeats, r(UUAGGG), is an integral component of the telomere and contributes to telomeric heterochromatin formation and telomere-length regulation. TERRA forms a G-quadruplex, but the biologic significance of its G-quadruplex formation is unknown. Compounds that selectively bind to G-quadruplex RNA are useful for understanding G-quadruplex TERRA. Here we report that an engineered RGG domain translocated in liposarcoma (TLS) specifically binds to G-quadruplex TERRA. The Arg-Gly-Gly repeat (RGG) TLS binds to G-quadruplex human telomere DNA and TERRA simultaneously, but we show that substitution of Tyr for Phe in the RGG domain of TLS (TLSRGG3Y) converts its binding specificity solely toward G-quadruplex TERRA. TLSRGG3Y binds to dG tetrads with abasic RNA loops, but fails to bind to rG tetrads without loops or dG tetrads with abasic DNA loops. These findings suggest that TLSRGG3Y binds to loops within the G-quadruplexes of TERRA by recognizing the 2'-OH of the riboses. To our knowledge, TLSRGG3Y is the first known molecule that specifically recognizes the 2'-OH of the riboses of loops in the G-quadruplex. TLSRGG3Y will be useful for investigating the role of the G-quadruplex form of TERRA without affecting G-quadruplex telomere DNA functions.
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: Takanori
authors.initials: T
authors.lastname: Oyoshi
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D054856:G-Quadruplexes; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D012266:Ribose / Q000737:chemistry / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D034702:RNA-Binding Protein FUS; D014443:Tyrosine; D012313:RNA; D012266:Ribose