title: Structure of long human telomeric RNA (TERRA): G-quadruplexes formed by four and eight UUAGGG repeats are stable building blocks.
abstract: The discovery of long RNA transcripts of telomeric repeats (TERRA) and their potential to form G-quadruplexes stimulated studies on the possible arrangements of G-quadruplexes along TERRA. Here we performed ribonuclease protection assay to investigate the structures formed by long human TERRA. We found that G-quadruplexes comprising four and eight UUAGGG repeats were most resistant to RNase T1 digestion, presumably with the former adopting an all-parallel-stranded propeller-type conformation and the latter forming a structure with two tandemly stacked G-quadruplex subunits each containing three G-tetrad layers. Molecular dynamics simulations of eight-repeat human TERRA sequences consisting of different stacking interfaces between the two G-quadruplex subunits, i.e., 5'-5', 3'-3', 3'-5', and 5'-3', demonstrated stacking feasibility for all but the 5'-3' arrangement. A continuous stacking of the loop bases from one G-quadruplex subunit to the next was observed for the 5'-5' stacking conformation. We also put forward other possible stacking arrangements that involve more than one linker connecting the two G-quadruplex subunits. On the basis of these results, we propose a "beads-on-a-string"-like arrangement along human TERRA, whereby each bead is made up of either four or eight UUAGGG repeats in a one- or two-block G-quadruplex arrangement, respectively.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
authors.forename: Herry
authors.initials: H
authors.lastname: Martadinata
authors.forename: Brahim
authors.initials: B
authors.lastname: Heddi
authors.forename: Kah Wai
authors.initials: KW
authors.lastname: Lim
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D054856:G-Quadruplexes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011188:Potassium; D012313:RNA / Q000737:chemistry* / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D006163:Ribonuclease T1 / Q000378:metabolism; D012996:Solutions; D016615:Telomere / Q000737:chemistry* / Q000235:genetics*
chemical_list: D012996:Solutions; D012313:RNA; D006163:Ribonuclease T1; D011188:Potassium