title: RNA secondary structure modeling at consistent high accuracy using differential SHAPE.
abstract: RNA secondary structure modeling is a challenging problem, and recent successes have raised the standards for accuracy, consistency, and tractability. Large increases in accuracy have been achieved by including data on reactivity toward chemical probes: Incorporation of 1M7 SHAPE reactivity data into an mfold-class algorithm results in median accuracies for base pair prediction that exceed 90%. However, a few RNA structures are modeled with significantly lower accuracy. Here, we show that incorporating differential reactivities from the NMIA and 1M6 reagents--which detect noncanonical and tertiary interactions--into prediction algorithms results in highly accurate secondary structure models for RNAs that were previously shown to be difficult to model. For these RNAs, 93% of accepted canonical base pairs were recovered in SHAPE-directed models. Discrepancies between accepted and modeled structures were small and appear to reflect genuine structural differences. Three-reagent SHAPE-directed modeling scales concisely to structurally complex RNAs to resolve the in-solution secondary structure analysis problem for many classes of RNA.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA.
authors.forename: Greggory M
authors.initials: GM
authors.lastname: Rice
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Leonard
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Weeks
mesh_terms: D000465:Algorithms; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*
chemical_list: D012313:RNA
keywords: accuracy; pseudoknot; sensitivity; thermodynamics
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