期刊
RNA
卷 20, 期 6, 页码 846-854出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.043323.113
关键词
accuracy; pseudoknot; sensitivity; thermodynamics
资金
- NSF [MCB-1121024]
- NIH [AI068462]
- NIH training grant in molecular and cellular biophysics [T32GM08570]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1121024] Funding Source: National Science Foundation
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.
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