Abstract
The discovery that certain small RNA molecules found in nature, viz. plant viroids, virusoids, and satellite RNAs, undergo spontaneous self-cleavage, has led to the design of short oligoribonucleotides that are able to function in trans as specific endoribonucleases (Uhlenbeck 1987; Haseloff and Gerlach 1988). The naturally occurring self-cleavage reaction plays a central role in the rolling circle replication of these pathogenic RNAs (Symons 1989). The so-called hammerhead model was proposed for the secondary structure of the self-cleaving domain consistent with many of these cleavage sites (Forster and Symons 1987), and is illustrated in Fig. 1 with the now standard numbering system (Hertel et al. 1992). The structure consists of three helices and a singlestanded loop of highly conserved residues (Keese and Symons 1987). Cleavage occurs after a NUX triplet, where N can be A, C, G, or U and X is not G, to generate a sequence terminating in the 2′,3′-cyclic phosphate of the X residue plus the 5′-hydroxy form of the second sequence. The trans cleaving structure can be formed from two RNA strands in a number of ways. The Uhlenbeck design in which the hammerhead motif is split through helices I and II (Uhlenbeck 1987), and the Haseloff and Gerlach design in which the motif is split between helices I and III as illustrated in Fig. 1 (Haseloff and Gerlach 1988). However, the Uhlenbeck style ribozymes have been shown to cleave substrates less efficiently than the Haseloff and Gerlach versions (Ruffner et al. 1989).
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Sproat, B.S. (1996). Synthetic Catalytic Oligonucleotides Based on the Hammerhead Ribozyme. In: Eckstein, F., Lilley, D.M.J. (eds) Catalytic RNA. Nucleic Acids and Molecular Biology, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61202-2_15
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DOI: https://doi.org/10.1007/978-3-642-61202-2_15
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