title: Structural characterization of a dimer of RNA duplexes composed of 8-bromoguanosine modified CGG trinucleotide repeats: a novel architecture of RNA quadruplexes.
abstract: Fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS) are neurodegenerative disorders caused by the pathogenic expansion of CGG triplet repeats in the FMR1 gene. FXTAS is likely to be caused by a 'toxic' gain-of-function of the FMR1 mRNA. We provide evidence for the existence of a novel quadruplex architecture comprising CGG repeats. The 8-bromoguanosine ((Br)G)-modified molecule GC(Br)GGCGGC forms a duplex in solution and self-associates via the major groove to form a four-stranded, antiparallel (GC(Br)GGCGGC)4 RNA quadruplex with (Br)G3:G6:(Br)G3:G6 tetrads sandwiched between mixed G:C:G:C tetrads. Self-association of Watson-Crick duplexes to form a four-stranded structure has previously been predicted; however, no experimental evidence was provided. This novel four-stranded RNA structure was characterized using a variety of experimental methods, such as native gel electrophoresis, NMR spectroscopy, small-angle X-ray scattering and electrospray ionization mass spectrometry.
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Noskowskiego 12/14, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Gudanis
authors.affiliation: NanoBioMedical Centre, Adam Mickiewicz University, 61-614 Poznan, Umultowska 85, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Popenda
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Noskowskiego 12/14, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Szpotkowski
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Noskowskiego 12/14, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Kierzek
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Noskowskiego 12/14, Poland zgdan@ibch.poznan.pl.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Gdaniec
mesh_terms: D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism; D054856:G-Quadruplexes; D015870:Gene Expression; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D006151:Guanosine; D012333:RNA, Messenger; C497683:FMR1 protein, human; C035169:8-bromoguanosine