A graph-based similarity approach to classify recurrent complex motifs from their context in RNA structures

This article proposes to use an RNA graph similarity metric, based on the MCES resolution problem, to compare the occurrences of specific complex motifs in RNA graphs, according to their context represented as subgraph. We rely on a new modeling by graphs of these contexts, at two different levels of granularity, and obtain a classification of these graphs, which is consistent with the RNA 3D structure. RNA many non-translational functions, as a ribozyme, riboswitch, or ribosome, require complex structures. Those are composed of a rigid skeleton, a set of canonical interactions called the secondary structure. Decades of experimental and theoretical work have produced precise thermodynamic parameters and efficient algorithms to predict, from sequence, the secondary structure of RNA molecules. On top of the skeleton, the nucleotides form an intricate network of interactions that are not captured by present thermodynamic models. This network has been shown to be composed of modular motifs, that are linked to function, and have been leveraged for better prediction and design. A peculiar subclass of complex structural motifs are those connecting RNA regions far away in the secondary structure. They are crucial to predict since they determine the global shape of the molecule, therefore important for the function. In this paper, we show by using our graph approach that the context is important for the formation of conserved complex structural motifs. We furthermore show that a natural classification of structural variants of the motifs emerges from their context. We explore the cases of three known motif families and we exhibit their experimentally emerging classification.