title: Stimulation of ribosomal frameshifting by RNA G-quadruplex structures.
abstract: Guanine-rich sequences can fold into four-stranded structures of stacked guanine-tetrads, so-called G-quadruplexes (G4). These unique motifs have been extensively studied on the DNA level; however, exploration of the biological roles of G4s at the RNA level is just emerging. Here we show that G4 RNA when introduced within coding regions are capable of stimulating -1 ribosomal frameshifting (-1 FS) in vitro and in cultured cells. Systematic manipulation of the loop length between each G-tract revealed that the -1 FS efficiency positively correlates with G4 stability. Addition of a G4-stabilizing ligand, PhenDC3, resulted in higher -1 FS. Further, we demonstrated that the G4s can stimulate +1 FS and stop codon readthrough as well. These results suggest a potentially novel translational gene regulation mechanism mediated by G4 RNA.
authors.affiliation: Department of Molecular Genetics, Leiden Institute of Chemistry, Leiden University, PO Box 9502, Leiden, The Netherlands and Institut Curie, UMR 176-CNRS, Bât 110, Université Paris-Sud, 91405 Orsay, France.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Yu
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.forename: René C L
authors.initials: RC
authors.lastname: Olsthoorn
mesh_terms: D020121:5' Untranslated Regions; D018388:Codon, Terminator; D018965:Frameshifting, Ribosomal; D054856:G-Quadruplexes; D008024:Ligands; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D020121:5' Untranslated Regions; D018388:Codon, Terminator; D008024:Ligands; D012313:RNA