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The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data

Abstract

The classical RNA secondary structure model considers A·U and G·C Watson–Crick as well as G·U wobble base pairs. Here we substitute it for a new one, in which sets of nucleotide cyclic motifs define RNA structures. This model allows us to unify all base pairing energetic contributions in an effective scoring function to tackle the problem of RNA folding. We show how pipelining two computer algorithms based on nucleotide cyclic motifs, MC-Fold and MC-Sym, reproduces a series of experimentally determined RNA three-dimensional structures from the sequence. This demonstrates how crucial the consideration of all base-pairing interactions is in filling the gap between sequence and structure. We use the pipeline to define rules of precursor microRNA folding in double helices, despite the presence of a number of presumed mismatches and bulges, and to propose a new model of the human immunodeficiency virus-1 -1 frame-shifting element.

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Figure 1: A selection of 3D structures predicted from sequence.
Figure 2: A selection of pre-miRNA 3D structures.
Figure 3: HIV-1 -1 frame-shifting-element models.

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Acknowledgements

We thank P. Thibault for updating MC-Sym and P. Gendron for helping us with the Condor and web services. We thank D. D’Amours, M.-F. Gaumont-Leclerc and V. Lisi for making suggestions to improve the manuscript. We thank D. H. Mathews and E. Westhof for discussions about MC-Fold. This project was supported by grants from the Canadian Institutes of Health Research (CIHR) and from the Natural Sciences and Engineering Research Council (NSERC) of Canada. M.P. holds Ph.D. scholarships from the NSERC and the Fonds Québécois de la Recherche sur la Nature et les Technologies. F.M. is a member of the Centre Robert-Cedergren of the Université de Montréal.

Author Contributions Both authors were involved in every aspect of the research. M.P. programmed MC-Fold and MC-Cons.

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Correspondence to François Major.

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The file contains Supplementary Methods, Supplementary Discussion, Supplementary Tables S1-S3, Supplementary Figures S1-S15 with Legends and additional references. (PDF 1907 kb)

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Parisien, M., Major, F. The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data. Nature 452, 51–55 (2008). https://doi.org/10.1038/nature06684

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