8DG7

Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex III

Summary for 8DG7

• Entry DOI: 10.2210/pdb8dg7/pdb
• EMDB information: 27417
• Descriptor: Endoribonuclease Dcr-1, RNA (22-MER), RNA (38-MER), ... (6 entities in total)
• Functional Keywords: dicer, dcr-1, loquacious, loqs-pb, mirna, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 4
• Total formula weight: 325153.46

Authors

Jouravleva, K.,Golovenko, D.,Demo, G.,Dutcher, R.C.,Tanaka Hall, T.M.,Zamore, P.D.,Korostelev, A.A. (deposition date: 2022-06-23, release date: 2022-11-16, Last modification date: 2024-06-12)

Primary citation

Jouravleva, K.,Golovenko, D.,Demo, G.,Dutcher, R.C.,Hall, T.M.T.,Zamore, P.D.,Korostelev, A.A.
Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB.
Mol.Cell, 82:4049-4063.e6, 2022

PubMed 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 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.

PubMed: 36182693
DOI: 10.1016/j.molcel.2022.09.002

Experimental method

ELECTRON MICROSCOPY (3.32 Å)