The tertiary structure and folding pathways of group II introns: paradigms for the assembly of large, multidomain RNAs and RNPs
Anna M. Pyle
Department of Molecular, Cellular and Developmental Biology and Department of Chemistry
Yale University
Group II introns are large ribozymes that catalyze their own self-splicing from precursor RNAs. The free introns can catalyze integration into duplex DNA through reverse-splicing reactions that can lead to intron mobility and retrotransposition within and among genomes. Group II introns therefore represent an important class of mobile genetic element that has played an important role in the evolution and diversification of terrestrial genomes. Based on their mechanistic and structural parallels with spliceosomal RNAs, they may also have played in important role in the evolution of eukaryotic RNA processing systems. In our laboratory, we study the tertiary structure and folding pathways of group II introns. We have found that group II introns can fold directly and faithfully to the native state through a series of obligate intermediates. Although group II introns can fold autonomously, certain proteins play a key stimulatory role during the various stages of folding and assembly in-vivo. We recently solved the crystal structure of a group II intron, which has revealed networks of tertiary interactions and scaffolding that are critical for folding, stability and catalysis. By examining the structure and kinetic properties of the folded intron, and of intermediates along the assembly pathway, we hope to define the driving forces for folding of large RNAs, and to describe the various ways that proteins facilitate this process.