Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB
| Autoři | |
|---|---|
| Rok publikování | 2022 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Molecular Cell |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.sciencedirect.com/science/article/pii/S109727652200853X?via%3Dihub |
| Doi | http://dx.doi.org/10.1016/j.molcel.2022.09.002 |
| Klíčová slova | COLI RIBONUCLEASE-IIIRNA-BINDINGCRYSTAL-STRUCTUREDOMAIN REVEALSTRBP COMPLEXRECOGNITIONMIRNASINTERFERENCEPREDICTIONMECHANISM |
| Popis | 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. Keywords |
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