A crystallographic and modelling study of a human telomeric RNA (TERRA) quadruplex

G.W. Collie, Shozeb Haider, S. Neidle, G.N. Parkinson

Research output: Contribution to journalArticlepeer-review

206 Citations (Scopus)

Abstract

DNA telomeric repeats in mammalian cells are transcribed to guanine-rich RNA sequences, which adopt parallel-stranded G-quadruplexes with a propeller-like fold. The successful crystallization and structure analysis of a bimolecular human telomeric RNA G-quadruplex, folded into the same crystalline environment as an equivalent DNA oligonucleotide sequence, is reported here. The structural basis of the increased stability of RNA telomeric quadruplexes over DNA ones and their preference for parallel topologies is described here. Our findings suggest that the 2'-OH hydroxyl groups in the RNA quadruplex play a significant role in redefining hydration structure in the grooves and the hydrogen bonding networks. The preference for specific nucleotides to populate the C3'-endo sugar pucker domain is accommodated by alterations in the phosphate backbone, which leads to greater stability through enhanced hydrogen bonding networks. Molecular dynamics simulations on the DNA and RNA quadruplexes are consistent with these findings. The computations, based on the native crystal structure, provide an explanation for RNA G-quadruplex ligand binding selectivity for a group of naphthalene diimide ligands as compared to the DNA G-quadruplex.
Original languageEnglish
Article numbergkq259
Pages (from-to)5569-5580
Number of pages12
JournalNucleic Acids Research
Volume38
Issue number16
DOIs
Publication statusPublished - 22 Apr 2010

ASJC Scopus subject areas

  • Genetics

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