Abstract
The hammerhead ribozyme is a small, self-cleaving genomic ribozyme whose substrate-targeting properties are quite flexible. It catalyzes a phosphodiester backbone cleavage reaction that can be exploited for antisense-type applications in which it is desirable to cleave the target RNA. To better understand the requirements for rational hammerhead ribozyme design, the natural history, secondary and tertiary structures, and reaction mechanism are reviewed in detail. Specifically, significant advances in our understanding of how the hammerhead ribozyme works have taken place since 2003, rendering previous assumptions about therapeutic hammerhead ribozyme design largely obsolete. The requirement for a tertiary contact between Stems I and II to be present in order to achieve a highly active ribozyme in vivo is described, and design requirements that enable straightforward incorporation of the tertiary contact are explicitly described. This analysis is only possible with crystal structures of two classes of full-length natural hammerhead ribozymes that became available in 2006 and 2008.
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Scott, W.G. (2010). What can the New Hammerhead Ribozyme Structures Teach us About Design?. In: Erdmann, V., Barciszewski, J. (eds) RNA Technologies and Their Applications. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12168-5_14
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DOI: https://doi.org/10.1007/978-3-642-12168-5_14
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