APPENDIX 2: RNA Pseudoknots

Understanding the many different biological activities displayed by RNA requires a detailed knowledge of the specific three-dimensional folding of a single-stranded RNA molecule. This folding is dominated by the formation of intramolecular double-helical or stem regions involving the Watson-Crick A • U and G • C base pairs. This gives rise to a collection of stems which is represented in what is called the “classical” or “orthodox” secondary structure of RNA. These structures have in common that loop regions formed (like hairpin [H], bulge [B], or interior [I] loops) do not participate in their turn in base-pairing. In the last decade it has become clear, however, that for the final, biologically relevant, tertiary structure, base-pairing of the loop regions can be essential. It is this kind of base-pairing that leads to the formation of pseudoknotted structures. Some basic features of possible pseudoknot structures are described here. For a more in-depth discussion of structural and functional aspects of RNA pseudoknots, see Westhof and Jaeger ( Curr. Opin. Struct. Biol. 2: 327 [1992]) and ten Dam et al. ( Biochemistry 31: 11665 [1992]). A pseudoknot structure is formed when a loop region in a classical secondary structure is involved in Watson-Crick base-pairing with a complementary region outside this loop. The simplest structural element in RNA is the hairpin and, consequently, base-pairing of the hairpin loop gives rise to the simplest type of pseudoknot (Fig. 1A). Base-pairing can take place with a sequence either downstream or upstream of the pseudoknot. Note that one single pseudoknot...