Nucleic Acids in Chemistry and Biology

ribosomal subunit contains a striking diversity of RNA triple interactions, one of which involves a network
of hydrogen bonds that are shared amongst all three nucleotides (Figure 7.4b).^5
Highly folded RNA molecules can contain quadruple interactionsor even larger arrays of hydrogen-
bonded bases. For example, an interesting quadruple variation is observed in the structure of a frameshift-
ing viral pseudoknot, that includes a protonated cytosine N-3 (Figure 7.5a).^6 Another remarkable
quadruple interaction occurs within an in vitro-selected aptamer, which consists of a central G base encir-
cled by hydrogen bonds to three other bases (Figure 7.5b).^7 An aptamer is an RNA or DNA molecule that
has been selected from a pool of random sequence, based on its ability to bind with high affinity to a par-
ticular ligand (Section 5.7.3).^8

7.1.4 RNA Tertiary Structure

7.1.4.1 Tertiary Structural Motifs. Although RNA molecules are commonly represented as two-

dimensional secondary structures, most RNAs are folded into compact and defined tertiary structures that
are necessary for function (Figure 7.6). Specific types of tertiary structures are seen for tRNA, rRNA,
snRNA, certain introns, and ribozymes.9,10But even mRNA can adopt complex tertiary structures, particu-
larly in the untranslated terminal regions (UTRs), which can be essential for proper gene expression.
One of the most important contributions to the three-dimensional form of a folded RNA is coaxial
stackingbetween adjacent sets of short RNA duplex,^11 for example as seen in a kissing hairpin complex
Figure 7.7. Among the most common substructures for stabilizing long-range interactions in RNA is the
tetraloop-receptormotif.^9 These involve a specific arrangement of base stacking and hydrogen bonds
between the GNRA tetraloop(a highly conserved loop with a defined structure) and a conserved stem-
loop sequence (Figure 7.8).
The A-minor motifis a ubiquitous interaction that involves contact between an adenosine and the
minor groove of a Watson–Crick base pair, thereby forming a type of triple interaction.^12 A-minor motifs
are observed in self-splicing introns and throughout the ribosome.^10 They can occur in isolation but are
often arranged in stacked arrays that may confer additional stabilization (Figure 7.9).

RNA Structure and Function 257

N

N N

N

O

N

C 1 '

NN

C 1 '

O

N

N

N

O

N

C 1 '

N

N

N

N

C 1 '

N

a

H

H H

H

H

H

H

H

H

H

N

N

N

N

C 1 '

N

O

N

N

NNC 1 '

N

N

N C 1 '

O

N

N

N N

N

C 1 '

O

N

b

H

H

H

H

H

H

H

H

H

H

Figure 7.5 Examples of quadruple interactions observed in RNA. (a) An ACGC quadruplex (ACGC amino-carbonyl,
amino(C)-N-7(G):N-3()C-carbonyl(G): carbonyl(C)-amino(C); Watson–Crick) from a frame-shifting
pseudoknot^6. (b) The GGCA quadruplex (GGCA imino-N-7, carbonyl-amino; Watson–Crick; N-3-
amino(G), amino-N-1(G)) from a dye-binding aptamer^7