Metabolite-binding ribozymes

Catalysis in the biological context was largely thought to be a protein-based phenomenon until the discovery of RNA catalysts called ribozymes. These discoveries demonstrated that many RNA molecules exhibit remarkable structural and functional versatility. By virtue of these features, naturally occurring ribozymes have been found to be involved in catalyzing reactions for fundamentally important cellular processes such as translation and RNA processing. Another class of RNAs called riboswitches directly binds ligands to control downstream gene expression. Most riboswitches regulate downstream gene expression by controlling premature transcription termination or by affecting the efficiency of translation initiation. However, one riboswitch class couples ligand-sensing to ribozyme activity. Specifically, the glmS riboswitch is a nucleolytic ribozyme, whose self-cleavage activity is triggered by the binding of GlcN6P. The products of this self-cleavage reaction are then targeted by cellular RNases for rapid degradation, thereby reducing glmS expression under conditions of sufficient GlcN6P. Since the discovery of the glmS ribozyme, other metabolite-binding ribozymes have been identified. Together, these discoveries have expanded the general understanding of noncoding RNAs and provided insights that will assist future development of synthetic riboswitch-ribozymes. A very broad overview of natural and synthetic ribozymes is presented herein with an emphasis on the structure and function of the glmS ribozyme as a paradigm for metabolite-binding ribozymes that control gene expression. This article is part of a Special Issue entitled: Riboswitches.