High salt solution structure of a left-handed RNA double helix.
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.
Laboratory of Structural Chemistry of Nucleic Acids, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12-14, 61-704 Poznań, Poland and Faculty of Chemistry, Adam Mickiewicz University, Poznań, Poland.
Mariusz
M
Popenda
Jan
J
Milecki
Ryszard W
RW
Adamiak
D020029:Base Pairing; D001483:Base Sequence; D003562:Cytidine / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000737:chemistry*; D010758:Phosphorus / Q000737:chemistry; D011522:Protons; D012330:RNA, Double-Stranded / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry
D009843:Oligoribonucleotides; D011522:Protons; D012330:RNA, Double-Stranded; C488537:tri(cytidylic acid-guanidylic acid); D010758:Phosphorus; D012965:Sodium Chloride; D003562:Cytidine