Analysis of secondary structural elements in human microRNA hairpin precursors.

Biao Liu,Dan Wang,Brent M Znosko,Steven M Gallo,Jessica L Childs-Disney,Matthew D Disney,Mohammad Fallahi

doi:10.1186/s12859-016-0960-6

Abstract

BackgroundMicroRNAs (miRNAs) regulate gene expression by targeting complementary mRNAs for destruction or translational repression. Aberrant expression of miRNAs has been associated with various diseases including cancer, thus making them interesting therapeutic targets. The composite of secondary structural elements that comprise miRNAs could aid the design of small molecules that modulate their function.ResultsWe analyzed the secondary structural elements, or motifs, present in all human miRNA hairpin precursors and compared them to highly expressed human RNAs with known structures and other RNAs from various organisms. Amongst human miRNAs, there are 3808 are unique motifs, many residing in processing sites. Further, we identified motifs in miRNAs that are not present in other highly expressed human RNAs, desirable targets for small molecules. MiRNA motifs were incorporated into a searchable database that is freely available.We also analyzed the most frequently occurring bulges and internal loops for each RNA class and found that the smallest loops possible prevail. However, the distribution of loops and the preferred closing base pairs were unique to each class.ConclusionsCollectively, we have completed a broad survey of motifs found in human miRNA precursors, highly expressed human RNAs, and RNAs from other organisms. Interestingly, unique motifs were identified in human miRNA processing sites, binding to which could inhibit miRNA maturation and hence function.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-0960-6) contains supplementary material, which is available to authorized users.

Highlights

MicroRNAs regulate gene expression by targeting complementary mRNAs for destruction or translational repression
In this study, we constructed a database of the secondary structural elements found in human miRNA hairpin precursor secondary structures
Analysis of this database reveals that small loops prevail in bulges and internal loops

Summary

Introduction

MicroRNAs (miRNAs) regulate gene expression by targeting complementary mRNAs for destruction or translational repression. Aberrant expression of miRNAs has been associated with various diseases including cancer, making them interesting therapeutic targets. MicroRNAs (miRNAs) regulate gene expression via targeting mRNAs for destruction or translation repression [1,2,3,4]. Different strategies have been used to inhibit oncogenic miRNAs, including antisense or sponge oligonucleotides that bind mature miRNAs [17, 18] and inhibiting miRNA processing with small molecules [19,20,21]. MiRNA hairpin precursors, which fold into stem loop structures that display various types of loops (Fig. 1) [25], are ideal candidates for small molecule binding. MiRNA processing occurs in both the nucleus (via Drosha) and the cytoplasm (via Dicer/transactivating response RNA-binding protein (TRBP)) [26]

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Conclusion