Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB.
Mol Cell
; 82(21): 4049-4063.e6, 2022 11 03.
Article
em En
| MEDLINE
| ID: mdl-36182693
ABSTRACT
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 LoqsPB 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 Dicer1â
LoqsPB heterodimer. The Dicer-1 dsRBD and three LoqsPB 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 Dicer1â
LoqsPB complex affects a complete cycle of pre-miRNA recognition, stepwise endonuclease cleavage, and product release.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Drosophila
/
MicroRNAs
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article