Structural Alignment of RNAs with Pseudoknots

Abstract

Non-coding RNAs (ncRNAs) are found to be critical for many biological processes. However, identifying these molecules is very difficult and challenging due to the lack of strong detectable signals such as opening read frames. Most computational approaches rely on the observation that the secondary structures of ncRNA molecules are conserved within the same family. Aligning a known ncRNA to a target candidate to determine the sequence and structural similarity helps in identifying de novo ncRNA molecules that are in the same family of the known ncRNA. However, the problem becomes more difficult if the secondary structure contains pseudoknots. Only until recently, many of the existing approaches could not handle structures with pseudoknots. This chapter reviews the state-of-the-art algorithms for different types of structures that contain pseudoknots including standard pseudoknot, simple non-standard pseudoknot, recursive standard pseudoknot, and recursive simple non-standard pseudoknot. Although none of the algorithms is designed for general pseudoknots, these algorithms already cover all known ncRNAs in both Rfam and PseudoBase databases. The evaluation of the algorithms also shows that the approach is useful in identifying ncRNA molecules in other species, which are in the same family of a known ncRNA.