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Structure paper

TitleStructural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB.
Journal, issue, pagesMol Cell, Vol. 82, Issue 21, Page 4049-44063.e6, Year 2022
Publish dateNov 3, 2022
AuthorsKarina Jouravleva / Dmitrij Golovenko / Gabriel Demo / Robert C Dutcher / Traci M Tanaka Hall / Phillip D Zamore / Andrei A Korostelev /
PubMed AbstractIn 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 ...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.
External linksMol Cell / PubMed:36182693 / PubMed Central
MethodsEM (single particle)
Resolution3.06 - 4.02 Å
Structure data

27415

8dfv

EMDB-27415, PDB-8dfv:
Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex IIa
Method: EM (single particle) / Resolution: 3.06 Å

27416

8dg5

EMDB-27416, PDB-8dg5:
Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex IIb
Method: EM (single particle) / Resolution: 3.26 Å

27417

8dg7

EMDB-27417, PDB-8dg7:
Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex III
Method: EM (single particle) / Resolution: 3.32 Å

27420

8dga

EMDB-27420, PDB-8dga:
Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex IV
Method: EM (single particle) / Resolution: 3.73 Å

27423

8dgi

EMDB-27423, PDB-8dgi:
Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex Ia
Method: EM (single particle) / Resolution: 3.94 Å

27427

8dgj

EMDB-27427, PDB-8dgj:
Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex Ib
Method: EM (single particle) / Resolution: 4.02 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-U5P:
URIDINE-5'-MONOPHOSPHATE / Uridine monophosphate

Source
  • drosophila melanogaster (fruit fly)
KeywordsRNA BINDING PROTEIN/RNA / Dicer / Dcr-1 / Loquacious / Loqs-P / miRNA / RNA BINDING PROTEIN-RNA complex / Loqs-PB

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