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You are here: Home / Teams / Complexity, plasticity, and functionality of miRNAs - K. Jouravleva / Publications / Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB

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

K. Jouravleva, D. Golovenko, G. Demo, R. C Dutcher, T. MT Hall, P. D Zamore, and A. A Korostelev (2022)

Mol Cell, 82(21):4049–4063.

In animals and plants, Dicer enzymes collaborate with double-stranded RNA-binding domain (dsRBD) proteins 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.

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