Jouravleva, KarinaGolovenko, DmitrijDemo, GabrielDutcher, Robert CHall, Traci M TanakaZamore, Phillip DKorostelev, Andrei A2023-01-302023-01-302022-09-30Jouravleva K, Golovenko D, Demo G, Dutcher RC, Hall TMT, Zamore PD, Korostelev AA. Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB. Mol Cell. 2022 Nov 3;82(21):4049-4063.e6. doi: 10.1016/j.molcel.2022.09.002. Epub 2022 Sep 30. PMID: 36182693; PMCID: PMC9637774.1097-416410.1016/j.molcel.2022.09.00236182693https://hdl.handle.net/20.500.14038/51609In 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.enCopyright 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Dcr-1DicerDicer-partner proteinsLoqs-PBLoquaciousRNase IIIcryo-EMdsRBDisomiRmiRNAmicroRNAJournal ArticleMolecular cell