High salt solution structure of a left-handed RNA double helix

Abstract

Right-handed RNA duplexes of (CG)n sequence undergo salt-induced helicity reversal, forming left-handed RNA double helices (Z-RNA). In contrast to the thoroughly studied Z-DNA, no Z-RNA structure of natural origin is known. Here we report the NMR structure of a half-turn, left-handed RNA helix (CGCGCG)2 determined in 6 M NaClO4. This is the first nucleic acid motif determined at such high salt. Sequential assignments of non-exchangeable proton resonances of the Z-form were based on the hitherto unreported NOE connectivity path [H6(n)-H5'/H5''(n)-H8(n+1)-H1'(n+1)-H6(n+2)] found for left-handed helices. Z-RNA structure shows several conformational features significantly different from Z-DNA. Intra-strand but no inter-strand base stacking was observed for both CpG and GpC steps. Helical twist angles for CpG steps have small positive values (4-7 degrees), whereas GpC steps have large negative values (-61 degrees). In the full-turn model of Z-RNA (12.4 bp per turn), base pairs are much closer to the helix axis than in Z-DNA, thus both the very deep, narrow minor groove with buried cytidine 2'-OH groups, and the major groove are well defined. The 2'-OH group of cytidines plays a crucial role in the Z-RNA structure and its formation; 2'-O-methylation of cytidine, but not of guanosine residues prohibits A to Z helicity reversal.

Double-stranded RNA under force and torque: Similarities to and striking differences from double-stranded DNA

“…S3L). We note that the helicity and elongation that we observe for L-RNA under torsional constraint are similar to what has been proposed for the NMR solution structure of a short (6-bp) GC-rich dsRNA fragment in 6 M monovalent salt (30). However, further investigation is necessary to elucidate structural details of torsionally strained left-handed dsRNA.…”

A nature of conformational changes of yeast tRNAPhe

“…It was shown by neutron diffraction that the salt ions induce a change in water structure equivalent to that of application of high pressure [29]. In RNA molecules, conformational changes were detected at 6 M NaClO 4 and 42 • C [30][31][32]. It has been shown experimentally and theoretically that water molecules, even located at long distances from the solute (>10Å), are structurally important [33,34].…”

Modified RNA with a Phosphate-Methylated Backbone. A Serious Omission in Our (Retracted) Study at HIV-1 RNA Loops and Integrated DNA. Specific Properties of the (Modified) RNA and DNA Dimers

“…The work of Davis et al, [18] and Popenda et al, [19] on the high salt structure of a left-handed RNA double helix is well-known. It was found that for the natural ribohexanucleotide r(C P G P C P G P C P G) at 1M concentration a duplex is formed with an A-conformation.…”

“…For the role of dispersion interactions it is necessary to have at one's disposal a representative model for the solely duplex-and filling-space structures of the aforementioned (modified) DNA and RNA. For the antiparallel phosphate-methylated DNA there is a self-complementary left-handed dimer d(C P G) [4], its (right-handed) tetramer d(C P G P C P G) [14], and the right-handed r(2ꞌ-OMe)C P G [19] available. The individual duplex structures were obtained from CD and NMR data, vide supra.…”