Discovery of selective, small-molecule inhibitors of RNA complexes—II. Self-splicing group I intron ribozyme Original Research Article

Self-splicing group I intron RNA was chosen as a potential therapeutic target for small-molecule intervention. High-throughput screening methodologies have been developed to identify small organic molecules that regulate the activities of these catalytic introns. Group I introns derived from pathogenic Pneumocystis carinii and phage T4 were used as model systems. Inhibitors identified from a library of ≈ 150,000 compounds were shown to regulate biochemical reactions including the two-step intron splicing and an RNA ligation catalyzed by the group I introns. These inhibitors provide a unique opportunity to understand small-molecule recognition of the self-splicing RNA. The methodologies developed for group I introns should be applicable to studies of other RNA systems.