Unlike DNA, RNA is normally single-stranded. The exception is provided by certain RNA viruses that have a double-stranded RNA genome. Double-stranded RNA is also transiently formed when some RNA viruses with a single-stranded RNA genome transcribe RNA sequences to make a complementary RNA. See Box 1.2 for the extraordinary variety of viral genomes.
To perform certain cell functions, different cellular RNA molecules may need to transiently associate by RNA–RNA base pairing, and some RNA sequences also engage with DNA sequences to form RNA–DNA duplexes. RNA–RNA and RNA–DNA duplexes can occur transiently within the context of gene regulation and transcription: many regulatory noncoding RNAs work by base pairing with target sequences in an RNA or DNA strand, and RNA–DNA helices are transiently formed during RNA synthesis when one DNA strand is used to make a complementary RNA, as described in the next section. The presence of a 2′ hydroxyl group on ribose sugars provides a structural constraint on the double helix of an RNA–RNA or an RNA–DNA duplex, so that an A-type double helix is formed rather than the common B-type double helix (Figure 1).
Fig1. Diversity in the structure of nucleic acid double helices. Shown here are three alternative structures of a double helix, in this case a DNA duplex. In addition to the B-form, the predominant form of DNA in cells under physiological conditions, the rare Z-form of DNA can also form in the case of certain sequences under certain physiological conditions (high salt concentrations). It has a narrower, more elongated helix. The A-form helix is shorter and wider than the B-form helix and has a deep, narrow major groove, which makes it less accessible to proteins. A-DNA only exists under nonphysiological conditions, but the presence of a 2′ hydroxyl group on the ribose sugar means that under physiological conditions both RNA RNA and RNA–DNA duplexes are constrained to form an A-form double helix. Pitch, distance per complete turn.
In addition to permitting RNA–RNA duplexes, and RNA–DNA duplexes, hydrogen bonding is crucially important in shaping the structure of a single-stranded RNA, and in allowing functional, short, double-stranded sequence motifs that can be recognized by specific RNA-binding proteins. Hairpin structures are the most common type of secondary structure motif (Figure 2A). Intrachain base pairing is extremely important in determining the shape of noncoding RNA and complex structures can form as a result, both in classical noncoding RNAs (Figure 2B) and in the noncoding untranslated regions of mRNAs.
Fig2. Highly-developed secondary structure in RNA due to intramolecular base pairing. (A) Examples of RNA secondary structure. A hairpin consists of a stem-and-loop arrangement formed when the RNA strand loops back to form a stem of laterally opposed bases that form base pairs, leaving a small loop of unpaired bases. Note that base pairing can include G-U base pairs (highlighted in yellow) as well as standard Watson–Crick base pairs. A pseudoknot is formed from a hairpin in which some bases in the loop engage in base pairing with another sequence on the RNA strand. (B) A very high degree of secondary structure can produce a very highly-folded structure, evident in the ribosomal RNA shown here (the 5′ and 3′ ends of the RNA are highlighted for clarity). Note that this is necessarily a two-dimensional representation of a complex three-dimensional structure.
Note that in addition to the expected A-U and G-C base pairs, G-U base pairing can occur in short regions of double-stranded RNA within an RNA strand (see, for example, the hairpin in Figure 1A). Although not particularly stable, G-U base pairing does not significantly distort the RNA–RNA helix.
