Structure and Folding of Group II Introns

Given the biotechnological and medical potentials that reside within RNA, it is important to understand the underlying principles of how RNA folds from a disordered state to the native productive state, thereby adopting its complex structure that is required for fulfilling its functions. In the past years considerable progress has been made in elucidating the folding pathways of large catalytic RNAs, including a ribozyme derived from the Sc. ai5 group II intron. This ribozyme folds slowly to the native state by an apparent two state mechanism. We now aim to monitor why folding of the Sc. ai5 intron is slow, even though it is not impaired by the formation of nonnative kinetic folding traps. There is evidence that slow folding could be due to the formation of a key tertiary structure element. One putative candidate for such a nucleation site for folding is the c-c1-c2 three-way junction in domain 1. Three-way junctions are a common building block in many RNAs and play a crucial role in their tertiary structure formation. In addition, group II introns have a conserved secondary structure and share a comparable array of long-range interactions. Thus, it is tempting to think that they follow a similar pathway to achieve the native structure. However, peripheral structures differ between members of the group II intron family and they could influence their folding pathways. Therefore, it will be interesting to determine the folding pathways of other group II introns as well. In brief, we expect that the anticipated project is at the heart of understanding RNA structure and its folding principles.