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Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex IIaStructural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex IIa
Structural highlights
Publication Abstract from PubMedIn 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 LoqsâPB 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 Dicerâ1â LoqsâPB heterodimer. The Dicer-1 dsRBD and three LoqsâPB 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 Dicerâ1â LoqsâPB complex affects a complete cycle of pre-miRNA recognition, stepwise endonuclease cleavage, and product release. Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB.,Jouravleva K, Golovenko D, Demo G, Dutcher RC, Hall TMT, Zamore PD, Korostelev AA Mol Cell. 2022 Nov 3;82(21):4049-4063.e6. doi: 10.1016/j.molcel.2022.09.002. Epub , 2022 Sep 30. PMID:36182693[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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