The architecture of the 10-23 DNAzyme and its implications for DNA-mediated catalysis
Jan Borggräfe, Christoph G.W. Gertzen, Aldino Viegas, Holger Gohlke, Manuel Etzkorn
DNAzymes are high precision catalysts assembled from short DNA sequences. The prominent RNA-cleaving 10-23 DNAzyme has eluted high-resolution characterisation attempts for decades. A comprehensive integrated structural biol- ogy approach could now change this situation and revealed a surprising but efficient molecular architecture. This struc- tural snapshot (a) elaborates on central aspects of the recent findings, (b) discusses their mechanistic implications and (c) 3 compares the new findings to similar established RNA-cleaving systems.
The 10-23 DNAzyme is among the most catalytically active DNA sequences and consists of two variable substrate-binding arms that can hybridise with a complementary RNA target, and a catalytic loop of 15 nucleotides, which cleaves the RNA target in an Mg2+-dependent manner.
Understanding the molecular features of catalytically active DNA sequences, so-called DNAzymes, is essential not only for our understanding of the fundamental properties of catalytic nucleic acids in general, but may well be the key to unravelling their full potential via tailored modifications. Our recent findings contributed to the endeavour to assemble a mechanistic picture of DNA-mediated catalysis by providing high-resolution structural insights into the 10-23 DNAzyme (Dz) and exposing a complex interplay between the Dz’s unique molecular architecture, conformational plasticity, and dynamic modulation by metal ions as central elements of the DNA catalyst. Here, we discuss key features of our findings and compare them to other studies on similar systems.
DNAzyme-based therapies could be applied to reduce expression levels of disease-related proteins, such as those involved in cancer, viral diseases or neurodegenerative diseases
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