Abstract

Graphical abstractSecondary structures of RNAs are crucial to the understanding of their tertiary structures and functions. At present, many theoretical methods are widely used to predict RNA secondary structures. The performance of these methods has been evaluated but only for their ability of base-pairing prediction. However, the topology of a RNA secondary structure is more important for understanding its tertiary structure and function, especially for long RNAs. In this paper, we constructed a new non-redundant RNA database containing 73 RNA with lengths of 50–300 nucleotides and benchmarked four popular algorithms for both base pairing and topology. The results show that the prediction accuracy of secondary structure topology is only 38%, in contrast to 70% for that of base pairing. Furthermore, the topological consistency is not strongly correlated to the base-pairing consistency. Our results will be helpful to understand the limitations of RNA secondary structure prediction methods from a different point of view and also to their improvements in future.

Highlights

  • It is recognized that RNA plays more important roles in the life process than expected (Li et al 2017; Zhao et al 2016)

  • Since RNA folding is considered as a hierarchical process (Tinoco and Bustamante 1999), most successful approaches of predicting RNA tertiary structures are based on secondary structures (Cao and Chen 2011; Popenda et al 2012; Wang et al 2015, 2017; Xu and Chen 2015; Zhao et al 2012) and this can improve the accuracy of RNA tertiary structure predictions significantly

  • The helical stems are formed by complementary canonical Watson–Crick and non-canonical Watson–Crick base pairs

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Summary

INTRODUCTION

It is recognized that RNA plays more important roles in the life process than expected (Li et al 2017; Zhao et al 2016). The physics-based free energy minimization approach of RNA secondary structure prediction is still widely used by biologists The performances of this type of secondary structure predictions have been evaluated previously and were found to be about 70% when comparing predicted and native base pairs on an RNA database without riboswitches and ribozymes (Mathews et al 2004; Xu et al 2012). Under such an accuracy of base-pair prediction, if using the predicted secondary structure information in the tertiary structure prediction, the topology of the former is critical to the performance of the latter. We analyze some possible reasons for the difficulties of the prediction of correct topologies of RNA secondary structures

RESULTS AND DISCUSSION
K4C tRNA
CONCLUSION
MATERIALS AND METHODS

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