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Regulation of splicing enhancer activities by RNA secondary structures.

ABSTRACT: In this report, we studied the effect of RNA structures on the activity of exonic splicing enhancers on the SMN1 minigene model by engineering known ESEs into different positions of stable hairpins. We found that as short as 7-bp stem is sufficient to abolish the enhancer activity. When placing ESEs in the loop region, AG-rich ESEs are fully active, but a UCG-rich ESE is not because of additional structural constraints. ESEs placed adjacent to the 3' end of the hairpin structure display high enhancer activity, regardless of their sequence identities. These rules explain the suppression of multiple ESEs by point mutations that result in a stable RNA structure, and provide an additional mechanism for the C6T mutation in SMN2.

SUBMITTER: Liu W

PROVIDER: S-EPMC6644664 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Regulation of splicing enhancer activities by RNA secondary structures.

Liu Wei W Zhou Yu Y Hu Zexi Z Sun Tao T Denise Alain A Fu Xiang-Dong XD Zhang Yi Y

FEBS letters 20101001 21

In this report, we studied the effect of RNA structures on the activity of exonic splicing enhancers on the SMN1 minigene model by engineering known ESEs into different positions of stable hairpins. We found that as short as 7-bp stem is sufficient to abolish the enhancer activity. When placing ESEs in the loop region, AG-rich ESEs are fully active, but a UCG-rich ESE is not because of additional structural constraints. ESEs placed adjacent to the 3' end of the hairpin structure display high enh ...[more]

PMID: 20888818

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Project description:BackgroundAccurate structure prediction methods play an important role for the understanding of RNA function. Energy-based, pseudoknot-free secondary structure prediction is one of the most widely used and versatile approaches, and improved methods for this task have received much attention over the past five years. Despite the impressive progress that as been achieved in this area, existing evaluations of the prediction accuracy achieved by various algorithms do not provide a comprehensive, statistically sound assessment. Furthermore, while there is increasing evidence that no prediction algorithm consistently outperforms all others, no work has been done to exploit the complementary strengths of multiple approaches.ResultsIn this work, we present two contributions to the area of RNA secondary structure prediction. Firstly, we use state-of-the-art, resampling-based statistical methods together with a previously published and increasingly widely used dataset of high-quality RNA structures to conduct a comprehensive evaluation of existing RNA secondary structure prediction procedures. The results from this evaluation clarify the performance relationship between ten well-known existing energy-based pseudoknot-free RNA secondary structure prediction methods and clearly demonstrate the progress that has been achieved in recent years. Secondly, we introduce AveRNA, a generic and powerful method for combining a set of existing secondary structure prediction procedures into an ensemble-based method that achieves significantly higher prediction accuracies than obtained from any of its component procedures.ConclusionsOur new, ensemble-based method, AveRNA, improves the state of the art for energy-based, pseudoknot-free RNA secondary structure prediction by exploiting the complementary strengths of multiple existing prediction procedures, as demonstrated using a state-of-the-art statistical resampling approach. In addition, AveRNA allows an intuitive and effective control of the trade-off between false negative and false positive base pair predictions. Finally, AveRNA can make use of arbitrary sets of secondary structure prediction procedures and can therefore be used to leverage improvements in prediction accuracy offered by algorithms and energy models developed in the future. Our data, MATLAB software and a web-based version of AveRNA are publicly available at http://www.cs.ubc.ca/labs/beta/Software/AveRNA.

Dataset Information

Regulation of splicing enhancer activities by RNA secondary structures.

Publications

Regulation of splicing enhancer activities by RNA secondary structures.

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