Nature 452, 51-55 (6 March 2008) | doi:10.1038/nature06684; Received 7 January 2007; Accepted 11 January 2008

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

Marc Parisien1 & Fran|[ccedil]|ois Major1

  1. Institute for Research in Immunology and Cancer (IRIC), Department of Computer Science and Operations Research, Universit|[eacute]| de Montr|[eacute]|al, PO Box 6128, Downtown Station, Montr|[eacute]|al, Qu|[eacute]|bec H3C 3J7, Canada

Correspondence to: Fran|[ccedil]|ois Major1 Correspondence and requests for materials should be addressed to F.M. (Email:


The classical RNA secondary structure model considers A|[middot]|U and G|[middot]|C Watson|[ndash]|Crick as well as G|[middot]|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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