Multiple RNA Interaction with Sub-optimal Solutions

The interaction of two RNA molecules involves a complex interplay between folding and binding that warranted recent developments in RNA-RNA interaction algorithms. However, biological mechanisms in which more than two RNAs take part in an interaction exist. It is reasonable to believe that interactions involving multiple RNAs are generally more complex to be treated pairwise. In addition, given a pool of RNAs, it is not trivial to predict which RNAs are interacting without sufficient biological knowledge. Therefore, structures resulting from multiple RNA interactions often cannot be predicted by the existing algorithms. We recently proposed a system for multiple RNA interaction that overcomes the difficulties mentioned above by formulating a combinatorial optimization problem called Pegs and Rubber Bands. A solution to this problem encodes a structure of interacting RNAs. In general, however, the optimal solution obtained does not necessarily correspond to the actual structure observed experimentally. Moreover, a structure produced by interacting RNAs may not be unique. In this work, we extend our previous approach to generate multiple sub-optimal solutions. By clustering these solutions, we are able to reveal representatives that correspond to realistic structures. Specifically, our results on the U2-U6 complex in the spliceosome of yeast and the CopA-CopT complex in E. Coli are consistent with published biological structures.