RNA Structure and Function 255
Figure 7.2 Hydration of RNA in the major (a) and minor (b) grooves in the crystal structure of the RNA duplex
[r(CCCCGGGG)] 2. In the major groove, water pentagons along strand 1 are red, along strand 2 they are
green, and water bridges between O-6 atoms of guanines are yellow and cyan in the top and bottom
halves of the duplex, respectively. In the minor groove, water bridges between 2-hydroxyl groups from
opposite strands within base-pair steps are red. Bridges between 2-hydroxyl groups within base-pair
planes and sharing a water molecule with the former bridges are cyan. Two water molecules and a
phosphate oxygen from an adjacent duplex link the hydroxyl groups of residues G7 and C11 and are
colored yellow
(Reprinted from Ref. 2. © (1996), with permission from the American Chemical Society)
behaves in this fashion. The hydrationproperties of RNA duplexes are also distinctive.^2 Complex net-
works of water molecules associate with both nucleobase and backbone atoms, resulting in a rich array of
functionalities for molecular recognition (Figure 7.2).
7.1.2 Base Pairings in RNA
Unlike DNA, RNA structures accommodate a variety of alternative base pairings.^3 In addition to the
canonical Watson–Crick G:C and A:U base pairs (Figure 2.8), a large variety of other base-pair combin-
ations are observed. The most common alternative pairings are the G:U wobble pairand the A:C pair
(Figure 7.3, see also Figure 2.9). The G:U pair is notable in that it provides a large hydrogen-bond donor
group (exocyclic amino) in the minor groove of RNA duplexes, which is an important recognition element
for proteins and other ligands. The G:U pair occurs in many biological contexts, including the codon–anti-
codon interactions that form the genetic code between tRNA and mRNA (Section 7.3). In the A:C pair,
the adenine N-1 is protonated as a result of a shift in pKathat can sometimes occur within folded RNA
structures. Shifts in pKadiversify the function of the four nucleobases and result in altered pairing as well
as chemical capabilities. The A:C pair is observed within some RNA loops and in the core of many cata-
lytic RNAs (ribozymes, Sections 7.2 and 7.6).
Purine nucleotides can also readily pair with one another. G:A pairsare common at the termini of RNA
helices, in loops and in folds that comprise RNA tertiary structure. While there are many types of G:A,
G:G, and A:A pairs, sheared G:A pairs are the most common (e.g., Figure 7.3), which include a Hoogsteen
interaction that involves the N-7 and 6-amino groups in the major groove edge of the A base (Figure 7.3).