Mechanistic Studies on Hammerhead Ribozymes

Abstract

Catalytic RNAs include group I and II introns; the RNA subunit of RNase P; hammerhead, hairpin, and hepatitis delta virus ribozymes; and ribosomal RNA (Altman 1989; Cech 1989; Michel et al. 1989; Noller et al. 1992; Symons 1992; Bratty et al. 1993; Gesteland and Atkins 1993). Of all these catalytic RNAs, the hammerhead ribozyme is the smallest. Naturally occurring hammerhead ribozymes were identified initially within RNA viruses and they act in cis during viral replication by the rolling circle mechanism (Symons 1989, 1992; Bratty et al. 1993). Hammerhead ribozymes have been engineered in such a way that they can act in trans to cleave other RNA molecules (Uhlenbeck 1987; Haseloff and Gerlach 1988). The trans-acting hammerhead ribozyme developed by Haseloff and Gerlach (1988) consists of an antisense section (stems I and III) and a catalytic domain with a flanking stem II and loop section (Fig. 1). Because of the small size of hammerhead ribozymes, they are very suitable for mechanistic studies, being good representatives of catalytic RNA.