Crystal structure of an RNA double helix incorporating a track of non-Watson–Crick base pairs

Abstract

The crystal structure of the RNA dodecamer duplex (r-GGACUUCGGUCC)2 has been determined. The dodecamers stack end-to-end in the crystal, simulating infinite A-form helices with only a break in the phosphodiester chain. These infinite helices are held together in the crystal by hydrogen bonding between ribose hydroxyl groups and a variety of donors and acceptors. The four noncomplementary nucleotides in the middle of the sequence did not form an internal loop, but rather a highly regular double-helix incorporating the non-Watson-Crick base pairs, G.U and U.C. This is the first direct observation of a U.C (or T.C) base pair in a crystal structure. The U.C pairs each form only a single base-base hydrogen bond, but are stabilized by a water molecule which bridges between the ring nitrogens and by four waters in the major groove which link the bases and phosphates. The lack of distortion introduced in the double helix by the U.C mismatch may explain its low efficiency of repair in DNA. The G.U wobble pair is also stabilized by a minor-groove water which bridges between the unpaired guanine amino and the ribose hydroxyl of the uracil. This structure emphasizes the importance of specific hydrogen bonding between not only the nucleotide bases, but also the ribose hydroxyls, phosphate oxygens and tightly bound waters in stabilization of the intramolecular and intermolecular structures of double helical RNA.

Genetic Evidence for Interaction between Cbp1 and Specific Nucleotides in the 5′ Untranslated Region of Mitochondrial Cytochrome b mRNA in Saccharomyces cerevisiae

“…Since the phenotype of the mutants with changes at these positions is exactly the same as that of a cbp1 mutant, the results suggest that the CCG is required for recognition of the RNA by Cbp1. Also, since the CCG sequence cannot form conventional base pairs with any other sequence in the COB 5Ј UTR sufficiency element due to the remarkable AU richness of the leader, we hypothesize that either Cbp1 is a sequence-specific singlestranded RNA-binding protein similar to Sm (19), heterogeneous nuclear ribonucleoprotein particle proteins (13), and U2AF (44) or the CCG sequence is in a secondary structure formed by non-Watson-Crick base pair interactions (17,25). Cbp1, however, does not contain the consensus RNA-binding motifs (2) found in many of the sequence-specific singlestranded RNA-binding proteins (13).…”

Flexibility of Short-Strand RNA in Aqueous Solution as Revealed by Molecular Dynamics Simulation: Are A-RNA and A´-RNA Distinct Conformational Structures?

“…[11][12][13] For example, from Protein Database Bank (PDB) and Nucleic Acid Database (NDB) survey data, the following three RNA molecules have been found to adopt the structural features of A'-RNA: the tridecamer r(UGAGCUUCGGCUC), the RNA dodecamer duplex (r-GGACUUCGGUCC) 2 and helix IV of 5S rRNA. 16,18,19 For later reference the helical parameters, groove widths and torsion angles of these structures are provided in Table 1, computed utilizing two common structural analysis programs 3DNA 20 and CURVES. 21,22 Understanding both the structure and dynamics of RNA molecules on the atomistic level is critical to gaining a clearer picture of their role and function as therapeutic agents in gene silencing.…”

1.76 Å Structure of a Pyrimidine Start Alternating A-RNA Hexamer r(CGUAC)dG

“…During the past decade other RNA crystal structures have been unravelled: the hammerhead ribozyme (Pley et al, 1994;Scott et al, 1995Scott et al, , 1996, the P4±P6 domain of group I intron (Cate et al, 1996) after the model of the entire intron was proposed by Michel & Westhof (1990), complexes of RNA with proteins (Rould et al, 1989;Ruff et al, 1991;Biou et al, 1994;Arnez & Steitz, 1994;Oubridge et al, 1994;Valegard et al, 1994) and duplex RNA (Dock-Bregeon et al, 1988Holbrook et al, 1991;Leonard et al, 1994;Betzel et al, 1994;Cruse et al, 1994;Portmann et al, 1995;Schindelin et al, 1995;Baeyens et al, 1995;. Complex RNA's, like tRNA, rRNA, ribozyme, have double helical stems, loops and other tertiary structures, while DNA's are commonly composed of duplexes.…”