Ligand‐dependent ribozymes

Abstract

The discovery of catalytic RNA (ribozymes) more than 30 years ago significantly widened the horizon of RNA-based functions in natural systems. Similarly to the activity of protein enzymes that are often modulated by the presence of an interaction partner, some examples of naturally occurring ribozymes are influenced by ligands that can either act as cofactors or allosteric modulators. Recent discoveries of new and widespread ribozyme motifs in many different genetic contexts point toward the existence of further ligand-dependent RNA catalysts. In addition to the presence of ligand-dependent ribozymes in nature, researchers have engineered ligand dependency into natural and artificial ribozymes. Because RNA functions can often be assembled in a truly modular way, many different systems have been obtained utilizing different ligand-sensing domains and ribozyme activities in diverse applications. We summarize the occurrence of ligand-dependent ribozymes in nature and the many examples realized by researchers that engineered ligand-dependent catalytic RNA motifs. We will also highlight methods for obtaining ligand dependency as well as discuss the many interesting applications of ligand-controlled catalytic RNAs. WIREs RNA 2017, 8:e1395. doi: 10.1002/wrna.1395 For further resources related to this article, please visit the WIREs website.

Highly motif- and organism-dependent effects of naturally occurring hammerhead ribozyme sequences on gene expression

“…In addition to their occurrence in nature, ribozymes have been utilised frequently for biotechnological tasks. For example, when coupled with an aptamer via a so-called communication module, ligand-dependent ribozymes have been engineered [15]. Such aptazymes have been used as versatile tools in synthetic biology.…”

Crucial Roles of Two Hydrated Mg2+ Ions in Reaction Catalysis of the Pistol Ribozyme

“…Small self-cleaving ribozymes catalyze site-specific cleavage of their own phosphodiester backbone.T hey are widely distributed in nature and are essential for rolling-circle-based replication of satellite and pathogenic RNAs. [1][2][3][4][5][6][7][8][9][10][11][12][13] Comparative genomic analysis led to the discovery of novel selfcleaving ribozymes,n amed twister,t wister-sister, pistol, and hatchet. [14,15] Forthe first three classes,the three-dimensional architectures [16][17][18][19][20][21][22][23][24][25] in pre-cleavage states were solved by X-ray crystallography,a nd very recently,a lso the first structure of ah atchet ribozyme (product) has been determined.…”

Crucial Roles of Two Hydrated Mg2+ Ions in Reaction Catalysis of the Pistol Ribozyme

“…Small self‐cleaving ribozymes catalyze site‐specific cleavage of their own phosphodiester backbone. They are widely distributed in nature and are essential for rolling‐circle‐based replication of satellite and pathogenic RNAs . Comparative genomic analysis led to the discovery of novel self‐cleaving ribozymes, named twister, twister‐sister, pistol, and hatchet .…”