Abstract

BackgroundDicer is necessary for the process of mature microRNA (miRNA) formation because the Dicer enzyme cleaves pre-miRNA correctly to generate miRNA with correct seed regions. Nonetheless, the mechanism underlying the selection of a Dicer cleavage site is still not fully understood. To date, several studies have been conducted to solve this problem, for example, a recent discovery indicates that the loop/bulge structure plays a central role in the selection of Dicer cleavage sites. In accordance with this breakthrough, a support vector machine (SVM)-based method called PHDCleav was developed to predict Dicer cleavage sites which outperforms other methods based on random forest and naive Bayes. PHDCleav, however, tests only whether a position in the shift window belongs to a loop/bulge structure.ResultIn this paper, we used the length of loop/bulge structures (in addition to their presence or absence) to develop an improved method, LBSizeCleav, for predicting Dicer cleavage sites. To evaluate our method, we used 810 empirically validated sequences of human pre-miRNAs and performed fivefold cross-validation. In both 5p and 3p arms of pre-miRNAs, LBSizeCleav showed greater prediction accuracy than PHDCleav did. This result suggests that the length of loop/bulge structures is useful for prediction of Dicer cleavage sites.ConclusionWe developed a novel algorithm for feature space mapping based on the length of a loop/bulge for predicting Dicer cleavage sites. The better performance of our method indicates the usefulness of the length of loop/bulge structures for such predictions.

Highlights

  • Dicer is necessary for the process of mature microRNA formation because the Dicer enzyme cleaves pre-miRNA correctly to generate miRNA with correct seed regions

  • We developed a novel algorithm for feature space mapping based on the length of a loop/bulge for predicting Dicer cleavage sites

  • In the 3p arm, the average prediction accuracy of our method reached 83.0%, whereas PHDCleav achieved up to 79.1% prediction accuracy. These results suggest that our method LBSizeCleav outperforms binary patterns of PHDCleav in predicting the position of Dicer cleavage sites

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Summary

Introduction

Dicer is necessary for the process of mature microRNA (miRNA) formation because the Dicer enzyme cleaves pre-miRNA correctly to generate miRNA with correct seed regions. Several studies have been conducted to solve this problem, for example, a recent discovery indicates that the loop/bulge structure plays a central role in the selection of Dicer cleavage sites. In accordance with this breakthrough, a support vector machine (SVM)-based method called PHDCleav was developed to predict Dicer cleavage sites which outperforms other methods based on random forest and naive Bayes. Dicer in various species may contain a different combination of these domains Among these domains, the PAZ domain, RNase III domain, and dsRND are responsible for the function of substrate cleavage [8]. The cleavage occurs near the end of the terminal loop of pre-miRNA, introducing a cut into the hairpin

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