The hammerhead ribozyme is a small RNA motif that
self cleaves at a specific phosphodiester bond to produce
2′,3′ cyclic phosphate and 5′ hydroxyl
termini (Hutchins et al., 1986; Forster & Symons, 1987a).
The secondary structure of the hammerhead consists of three
helices of arbitrary sequence and length (designated I,
II, and III) that intersect at 15 nucleotides termed the
catalytic core (Fig. 1A) (Forster & Symons, 1987b;
Hertel et al., 1992). The X-ray crystal structures of two
hammerhead ribozyme–inhibitor complexes revealed
that the core residues fold into two separate domains and
the helices are arranged in a Y-shape conformation with
helix I and helix II forming the upper portion of the Y
(Pley et al., 1994; Scott et al., 1995). Although the hammerhead
is found as an intramolecular motif embedded in several
RNAs in vivo (Symons, 1989), it can be assembled from two
separate oligonucleotides (Fig. 1B) in three different
arrangements (Uhlenbeck, 1987; Haseloff & Gerlach,
1988; Koizumi et al., 1988; Jeffries & Symons, 1989).
In these bimolecular formats, the hammerhead effects RNA
cleavage in a similar manner to a true “enzyme,”
proceeding through multiple rounds of substrate binding,
cleavage, and product release (Uhlenbeck, 1987).