Abstract
While understanding the structure of RNA molecules is vital for deciphering their functions, determining RNA structures experimentally is exceptionally hard. At the same time, extant approaches to computational RNA structure prediction have limited applicability and reliability. In this paper we provide a method to solve a simpler yet still biologically relevant problem: prediction of secondary RNA structure using structure of different molecules as a template. Our method identifies conserved and unconserved subsequences within an RNA molecule. For conserved subsequences, the template structure is directly transferred into the generated structure and combined with de-novo predicted structure for the unconserved subsequences with low evolutionary conservation. The method also determines, when the generated structure is unreliable. The method is validated using experimentally identified structures. The accuracy of the method exceeds that of classical prediction algorithms and constrained prediction methods. This is demonstrated by comparison using large number of heterogeneous RNAs. The presented method is fast and robust, and useful for various applications requiring knowledge of secondary structures of individual RNA sequences.
Highlights
Despite recent improvements [SHAPE-seq (Loughrey et al, 2014), PARS (Kertesz et al, 2010), and FragSeq (Underwood et al, 2010)], experimental identification of RNA structures is technically demanding and only a limited number of RNA structures has been resolved
The main improvement is the ability to generate both large structures of long sequences and structures with long single-strand segments that are notoriously hard to be predicted with available prediction methods
A method for template–based prediction/generation of single-sequence secondary RNA structure is presented. It is useful for determining whether an RNA molecule under investigation can conform to a secondary structure taken from a different molecule
Summary
Despite recent improvements [SHAPE-seq (Loughrey et al, 2014), PARS (Kertesz et al, 2010), and FragSeq (Underwood et al, 2010)], experimental identification of RNA structures is technically demanding and only a limited number of RNA structures has been resolved. Known methods in both categories are unreliable for longer sequences (∼ >150 nucleotides) and more complex structures, e.g., those that contain longer single-stranded segments. This is owing to the extreme theoretical complexity of the prediction. The number of experimentally identified RNA structures is growing in spite of the technical demands. These structures are available as potential templates to generate secondary structures of uncharacterized but related RNA sequences.
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