The vast majority of our gene products are noncoding RNA molecules, many of which have elaborate three-dimensional structures. Despite the importance of RNA tertiary structure in gene expression, the scope of our knowledge about RNA structure and molecular recognition is limited. This is largely due to the small number of high resolution RNA structures and a paucity of studies on small molecule recognition by RNA. To address this problem, we have focused on understanding the molecular architecture and catalytic mechanism of group II introns, which are RNAs that catalyze their own splicing. We have also used the catalytic activity of group II introns to carry out high throughput screening of small molecule inhibitors, which we have optimized and developed as antifungal agents. These studies have been complemented by parallel studies on other long noncoding RNAs that lack catalytic activity, with the goal of identifying approaches for understanding and targeting RNA tertiary structures within the large network of regulatory lncRNAs.








Anna Marie Pyle (Yale University)