Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB

In animals and plants, Dicer enzymes collaborate with double-stranded RNA-binding domain (dsRBD) pro-teins to convert precursor-microRNAs (pre-miRNAs) into miRNA duplexes. We report six cryo-EM structures of Drosophila Dicer-1 that show how Dicer-1 and its partner Loqs-PB cooperate (1) before binding pre-miRNA, (2) after binding and in a catalytically competent state, (3) after nicking one arm of the pre-miRNA, and (4) following complete dicing and initial product release. Our reconstructions suggest that pre-miRNA binds a rare, open conformation of the Dicer-1???Loqs-PB heterodimer. The Dicer-1 dsRBD and three Loqs-PB dsRBDs form a tight belt around the pre-miRNA, distorting the RNA helix to place the scissile phosphodiester bonds in the RNase III active sites. Pre-miRNA cleavage shifts the dsRBDs and partially closes Dicer-1, which may promote product release. Our data suggest a model for how the Dicer-1???Loqs-PB complex affects a complete cycle of pre-miRNA recognition, stepwise endonuclease cleavage, and product release.

Automated summary

The study of the structures of Drosophila Dicer-1 reveals the collaborative mechanism of Dicer-1 and Loqs-PB in different stages, including before and after pre-miRNA binding, as well as after cleavage and product release. The findings suggest that the Dicer-1???Loqs-PB complex plays a crucial role in specific binding and cleavage of pre-miRNA, facilitating product release.