Abstract
Non-coding RNAs (ncRNAs) are receiving more and more attention not only as an abundant class of genes, but also as regulatory structural elements (some located in mRNAs). A key feature of RNA function is its structure. Computational methods were developed early for folding and prediction of RNA structure with the aim of assisting in functional analysis. With the discovery of more and more ncRNAs, it has become clear that a large fraction of these are highly structured. Interestingly, a large part of the structure is comprised of regular Watson-Crick and GU wobble base pairs. This and the increased amount of available genomes have made it possible to employ structure-based methods for genomic screens. The field has moved from folding prediction of single sequences to computational screens for ncRNAs in genomic sequence using the RNA structure as the main characteristic feature. Whereas early methods focused on energy-directed folding of single sequences, comparative analysis based on structure preserving changes of base pairs has been efficient in improving accuracy, and today this constitutes a key component in genomic screens. Here, we cover the basic principles of RNA folding and touch upon some of the concepts in current methods that have been applied in genomic screens for de novo RNA structures in searches for novel ncRNA genes and regulatory RNA structure on mRNAs. We discuss the strengths and weaknesses of the different strategies and how they can complement each other.
Highlights
Non-coding RNA genes have emerged as major players in the cell and are involved in both housekeeping functions as well as regulation
The current algorithmic approaches using sequence-based alignments are much faster than using structural alignments [42]; structural alignments can take regions with weak sequence conservation into account more accurately
An observation from the CMfinder screen on the ENCODE regions was that the CMfinder alignment was similar to the original alignment for MAF blocks with high sequence similarity, but showed significant rearrangement for low similarity blocks [101]
Summary
Non-coding RNA genes (ncRNAs) have emerged as major players in the cell and are involved in both housekeeping functions as well as regulation. In order to find ncRNA genes, it makes sense to search for RNA (secondary) structure rather than primary sequence.
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