RESUMO
Non-coding RNAs play a major role in diverse processes in living cells with their sequence and spatial structure serving as the principal determinants of their function. Superposition of RNA 3D structures is the most accurate method for comparative analysis of RNA molecules and for inferring structure-based sequence alignments. Topology-independent superposition is particularly relevant, as evidenced by structurally similar RNAs with sequence permutations such as tRNA and Y RNA. To date, state-of-the-art methods for RNA 3D structure superposition rely on intricate heuristics, and the potential for topology-independent superposition has not been exhausted. Recently, we introduced the ARTEM method for unrestrained pairwise superposition of RNA 3D modules and now we developed it further to solve the global RNA 3D structure alignment problem. Our new tool ARTEMIS significantly outperforms state-of-the-art tools in both sequentially-ordered and topology-independent RNA 3D structure superposition. Using ARTEMIS we discovered a helical packing motif to be preserved within different backbone topology contexts across various non-coding RNAs, including multiple ribozymes and riboswitches. We anticipate that ARTEMIS will be essential for elucidating the landscape of RNA 3D folds and motifs featuring sequence permutations that thus far remained unexplored due to limitations in previous computational approaches.
RESUMO
Understanding the 3D structure of RNA is key to understanding RNA function. RNA 3D structure is modular and can be seen as a composition of building blocks of various sizes called tertiary motifs. Currently, long-range motifs formed between distant loops and helical regions are largely less studied than the local motifs determined by the RNA secondary structure. We surveyed long-range tertiary interactions and motifs in a non-redundant set of non-coding RNA 3D structures. A new dataset of annotated LOng-RAnge RNA 3D modules (LORA) was built using an approach that does not rely on the automatic annotations of non-canonical interactions. An original algorithm, ARTEM, was developed for annotation-, sequence- and topology-independent superposition of two arbitrary RNA 3D modules. The proposed methods allowed us to identify and describe the most common long-range RNA tertiary motifs. Along with the prevalent canonical A-minor interactions, a large number of previously undescribed staple interactions were observed. The most frequent long-range motifs were found to belong to three main motif families: planar staples, tilted staples, and helical packing motifs.