MicroRNAs are shown to play a critical role in several developmental and differentiation processes. However, little is known about the maturation process of primary microRNAs (pri-miRNAs) at the molecular level or the role their secondary structures play in targeting them to the Microprocessor complex for maturation. The combination of SHAPE chemistry and MC-Pipeline modeling was used to determine the secondary structures of pri-miRNAs, which were found to feature extensive deformability in the stem adjacent to the Drosha cut site nearest the single-stranded: double-stranded junction; this provides a recognition site for the Microprocessor, which was confirmed by Drosha cleavage assays. In addition, binding studies using circular dichroism and gel shift assays were used to quantify the nature of the Microprocessor component DGCR8's interaction with pri-miRNAs. This study therefore has the ability to distinguish the catalytic effects of Drosha from the binding abilities of DGCR8 resulting from structure differences of various pri-miRNAs.

Primary microRNA structure and its recognition by the microprocessor

245th National Meeting (2013)

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