Structures of microRNA precursors

Abstract

MicroRNAs are single-stranded regulatory RNAs of 18-25 nucleotide length generated from endogenous transcripts that form local hairpin structures. The processing of microRNA transcripts involves the activities of two RNase III enzymes Drosha and Dicer. In this study we analyzed structural features of human microRNA precursors that make these transcripts Drosha and Dicer substrates. The structures of minimal functional primary precursors (pri-microRNAs) and secondary precursors (pre-microRNAs) were predicted. The frequency, nucleotide sequence content and the localization of various structure destabilizing motifs was analyzed. We identified numerous pri-microRNAs which structures strongly depart from the consensus structure and their processing is hard to explain by the existing model of the Microprocessor complex. We also found a biased distribution of symmetric and asymmetric motifs along the pre-microRNA hairpin stem and an over-representation of bulges on its 5′ arm (p < 0.000001), which may have considerable functional implications.