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

Warning

This publication doesn't include Faculty of Arts. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.

Authors	JOURAVLEVA Karina GOLOVENKO Dmitrij DEMO Gabriel DUTCHER Robert C HALL Traci M Tanaka ZAMORE Phillip D KOROSTELEV Andrei A
Year of publication	2022
Type	Article in Periodical
Magazine / Source	Molecular Cell
MU Faculty or unit	Central European Institute of Technology
Citation
Web	https://www.sciencedirect.com/science/article/pii/S109727652200853X?via%3Dihub
Doi	http://dx.doi.org/10.1016/j.molcel.2022.09.002
Keywords	COLI RIBONUCLEASE-IIIRNA-BINDINGCRYSTAL-STRUCTUREDOMAIN REVEALSTRBP COMPLEXRECOGNITIONMIRNASINTERFERENCEPREDICTIONMECHANISM
Description	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
Related projects:	Crosstalk between transcription and translation