Section 22.2.6.  Hydrogen bonding in nucleic acids

DNA structure is dominated by the prevalence of duplex structures and hence by the classic Watson–Crick hydrogen-bonding pattern of A–T and G–C base pairs. This hydrogen-bonding pattern is not affected by whether the double helix has A-form, B-form, or Z-form geometry. Other hydrogen-bonding modes in DNA are probably very rare, arising only as a result of mutations (which produce mismatches), chemical modifications, such as methylation, or other disturbances, such as the binding of drugs or proteins so as to alter DNA conformation. Mismatches can give stable hydrogen bonding but at the expense of local perturbations of the DNA structure.

In contrast to DNA, RNA molecules generally form single-stranded structures, which are correspondingly much more complex and less regular. This means that catalytic and other activities can be generated in addition to their information-carrying roles. Current knowledge of detailed RNA three-dimensional structure is limited to transfer RNAs and several ribozymes, including a large ribosomal RNA domain (Cate et al., 1996). Even from this small sample, however, it is clear that a great diversity of hydrogen-bonding interactions exists; RNA molecules contain regions of double-helical structure, often with classical Watson–Crick A–U and G–C base pairing, but these regions are interspersed with loops and bulges and tertiary interactions between the various secondary-structural (double-helical) elements. These interactions include many unconventional base pairings (e.g. see Fig. 22.2.6.1).

Figure 22.2.6.1| top | pdf | Hydrogen-bonding interactions in RNA tertiary structure. In (a), a triple base interaction is shown. In (b), G150 and A153 of a GAAA tetraloop participate in multiple hydrogen-bond interactions involving bases, riboses and phosphate. Reprinted with permission from Cate et al. (1996). Copyright (1996) American Association for the Advancement of Science.

Some RNA structural motifs may prove to be of widespread general importance in RNA molecules. One example is a sharp turn with sequence CUGA in the hammerhead ribozyme that exactly matches turns in tRNAs (Pley et al., 1994). Another is the GNRA tetraloop structure (N = any base, R = purine). This loop has a well defined structure, stabilized by hydrogen bonding and stacking involving its own bases, and it also presents further hydrogen-bonding groups that can dock into `receptor' structures in other parts of the RNA molecule. This results in triple or quadruple base interactions (Fig. 22.2.6.1) that tie different parts of the RNA structure together; the parallel with hydrogen-bonding side chains in proteins is very strong. The 2′-hydroxyls of ribose groups are also used in some of these interactions (Fig. 22.2.6.1). Further ribose interactions involve interdigitated ribose groups that line the interfaces between adjacent helices such that pairs of riboses interact by hydrogen bonding through their 2′-hydroxyl groups, forming `ribose zippers' As many more RNA structures are determined experimentally, it is likely that more hydrogen-bonding motifs will be recognized, and their full role in RNA structure can be better assessed than at our present, imperfect state of knowledge.