Grant: Project Grant

RNA controls gene expression through a number of different mechanisms, and disruptions of RNA-dependent events are directly linked to several human diseases. In addition, RNA molecules, such as ribozymes and riboswitches, are being increasingly exploited for biotechnology and therapeutic applications. Ribozymes are RNA enzymes that cleave specific RNA sequences and, thus, have the potential to be engineered to selectively inactivate a target gene. Riboswitches are RNA regulatory elements that modulate gene expression in response to metabolite binding. Most riboswitches have been found in bacteria and, thus, inhibiting their function represents an ideal approach for the development of novel antibiotics against pathogenic bacteria. The overall objective of this proposal is to continue our structure-function studies of ribozymes and riboswiches in order to help develop RNA-based therapeutics and diagnostic agents. More specifically, we propose to 1) Structurally investigate the Neurospora VS ribozyme; 2) Conduct engineering studies of the VS ribozymes; and 3) Structurally investigate the interaction between purine riboswitches and agonist compounds with antibiotic properties. Our proposed investigations will reveal important structure-function aspects of both purine riboswitches and the VS ribozyme. In addition, they will assist in the development of novel antibiotics that target RNA and help derive principles of RNA engineering that will be valuable in the development of RNA-based tools for biochemical and biomedical applications.