Abstract

BackgroundRNA secondary structure plays a scaffolding role for RNA tertiary conformation. Accurate secondary structure prediction can not only identify double-stranded helices and single stranded-loops but also help provide information for potential tertiary interaction motifs critical to the 3D conformation. The average accuracy in ab initio prediction remains 70%; performance improvement has only been limited to short RNA sequences. The prediction of tertiary interaction motifs is difficult without multiple, related sequences that are usually not available. This paper presents research that aims to improve the secondary structure prediction performance and to develop a capability to predict coaxial stacking between helices. Coaxial stacking positions two helices on the same axis, a tertiary motif present in almost all junctions that account for a high percentage of RNA tertiary structures.ResultsThis research identified energetic rules for coaxial stacks and geometric constraints on stack combinations, which were applied to developing an efficient dynamic programming application for simultaneous prediction of secondary structure and coaxial stacking. Results on a number of non-coding RNA data sets, of short and moderately long lengths, show a performance improvement (specially on tRNAs) for secondary structure prediction when compared with existing methods. The program also demonstrates a capability for prediction of coaxial stacking.ConclusionsThe significant leap of performance on tRNAs demonstrated in this work suggests that a breakthrough to a higher performance in RNA secondary structure prediction may lie in understanding contributions from tertiary motifs critical to the structure, as such information can be used to constrain geometrically as well as energetically the space of RNA secondary structure.

Highlights

  • RNA secondary structure plays the critical role of scaffolding the tertiary structure (i.e., 3D conformation) [1,2,3,4,5]

  • RNAcoast captured the secondary structure topology correctly for more than 72% of sequences. We carefully examined those sequences whose topologies were not predicted correctly and were able to identify that half of them have a long variable loop

  • This work introduced a new method for simultaneous prediction of RNA secondary structure and coaxial stacking between helices

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Summary

Introduction

RNA secondary structure plays the critical role of scaffolding the tertiary structure (i.e., 3D conformation) [1,2,3,4,5]. In the past three decades, considerable success has been made in Elements of the secondary structure are interrelated with tertiary interaction motifs [2,4,19], which consist of less understood non-canonical base pairs, with some just being revealed recently [19,20] Such motifs bundle and connect helices to form and stabilize the tertiary structure. Coaxial helices are prevalent in known RNA tertiary structures, for instance accounting for 32% of 613 tertiary interactions in 54 high-resolution RNA structures investigated by Schlick group [23] They are present at about 84% of multiple loop junctions involved in these structures. Coaxial stacking positions two helices on the same axis, a tertiary motif present in almost all junctions that account for a high percentage of RNA tertiary structures

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